This report refers to male patients of unknown age enrolled in a not blinded other studies. The objective of the study is to examine the effectiveness of PPV among approximately 40,000 community-dwelling men aged 45 years and older in the Men's Health Study cohort. All participants completed an extensive questionnaire at baseline (2002-2003) and were followed for the occurrence of invasive pneumococcal disease (IPD) or all-cause pneumonia hospitalization through the end of 2009. Immunization status and incident IPD and pneumonia cases were ascertained through electronic medical records. The associations between vaccination and IPD or pneumonia hospitalization were assessed using time-dependent Cox proportional models to account for socio-demographics, time-updated vaccination status and comorbidities. The median follow-up period of the 39,222 participants was 7.3 years. Among them, 11,902 (30.3%) had received at least one PPV vaccine at baseline and 7653 (19.5%) received their first PPV vaccine during the follow-up. There were 17 pneumococcal bacteremia cases, 647 hospitalized pneumonia cases, and no pneumococcal meningitis cases. Among the 647 men with a record of pneumonia hospitalization, 177 (27.4%) never received PPV, 250 (38.6%) received PPV at age <65 years, 158 (24.4%) received only at age >=65 years, and 62 (9.6%) had records showing received PPV before and after age 65 years. The results suggested a reduced risk of pneumococcal bacteremia among men vaccination at age >=65 (adjusted hazard ratio [HR]: 0.25% confidence interval [Cl}: 0.06-1.91; P=0.22). PPV vaccination did not show a protective effect against all-cause pneumonia hospitalization (adjusted HR: 1.18; 95% Cl: 1.02-1.37, p = 0.03) among men vaccinated before 65 years old, but a moderate protective effect was suggested among men without chronic obstructive pulmonary diseases who were vaccinated after 65 years old (adjusted HR: 0.84%: 95% Cl: 0.67-1.06. p = 0.15). The study based in an existing prospective cohort, which provides an opportunity to examine the association between pneumococcal vaccination and IPO and hospitalization for pneumonia. In this large, multi-ethic cohort of men, there was no indication of a benefit of PPV vaccination for hospitalization of all-cause pneumonia. A reduced risk of pneumococcal bacteremia (adjusted HR=0.35) associated with PPV vaccination was suggested among those who received the vaccine at age 65 years or older. However, the observed association was not statistically and the confidence intervals were wide. There might not be adequate statistical power to detect a statistically significant association despite a potential protective effect given the very small number of IPO cases (17 incident pneumococcal bacteremia cases, no pneumococcal meningitis case) in this insured population. Results from observational studies have been fairly consistent regarding the protective effect of PPV against IPO in immunocompetent older adults. In the recent Cochrane review, the authors concluded that non-randomized studies provided evidence supporting the recommendation for PPV to prevent IPO in adults. However, the evidence from randomized controlled trial was less clear with respect to adults with chronic illness. The authors suggested this might be due to either lack of effect or lack of power in the studies. Estimates of the effect of vaccine received before age 65 years are complicated by the difficulty in controlling for confounding by indication because the underlying risk differs greatly between those who received PPV and those who were unvaccinated before age 65 years. In general, unvaccinated men in this study tended to be younger, healthier, and have fewer co-morbid conditions at baseline compared to those who received the vaccine. This is consistent with the clinical guidelines in which the vaccine is recommended for adults aged 65 years and older and persons under age 65 years and older and persons under age 65 who have chronic cardiovascular disease (e.g., congestive heart failure or cardiomyopathy), chronic pulmonary diseases (e.g., chronic obstructive pulmonary disease or emphysema), or chronic liver diseases (e.g., cirrhosis), and diabetes mellitus. Thus, the observed association of PPV vaccination with increased risk of all-cause pneumonia hospitalization (adjusted HR: 1.18; 95% CI: 1.02-1.37, p=0.03) among those who received PPV before age 65 might suggest that men vaccinated before age 65 had higher risk for pneumococcal infections due to various chronic conditions or compromised immune functions and thus a suboptimal vaccine response. A statistically non-significant protection against pneumococcal bacteremia in men vaccinated at age 65 years or older was suggested. Similarly, a moderate protection against hospitalization for all-cause pneumonia was suggested among men vaccinated at age 65 years or older who had no COPO at baseline. These findings might suggest that the clinical effectiveness of PPV is more prominent among relatively healthy vaccines and it is unclear whether the vaccine could provide adequate protection among individuals with underlying conditions that might have substantially increased the risk for pneumococcal infections and/or compromised vaccine response. Although residual confounding could still affect our results, the investigators attempted to control for a number of potential confounders, along with additional adjustment for the propensity score, to account for the underlying differences between vaccinated and unvaccinated subjects in the analysis. In the subgroup analyses by COPO status at baseline, there was no evidence of a protective effect of PPV for either pneumococcal bacteremia or all-cause pneumonia hospitalization across these groups. Importantly, the outcomes were derived from the electronic health record, with the codes entered prospectively by the provider and professional coders, but not from billing data. It is likely that ascertainment/diagnosis of hospitalized IPO and pneumococcal bacteremia cases would be non-differential with respect to pneumococcal vaccination status, so that detection bias is probably negligible in this current study. Because the diagnostic codes of pneumonia might not be sufficiently sensitive, the investigators also used a broader set of ICO-9 diagnostic codes to identify pneumonia (480-487) but with no change to the results. The history of vaccines delivered outside the health plan system is mostly based on patient report therefore some vaccination may not be captured in our system. An estimated 95% of PPV doses captured in the data were delivered within the KPSC system based on the vaccine lot numbers entered in the vaccine tracking system. In the other large cohort study in the U.S. that assessed 47, 365 adults aged 65 years and old for a 3 year period, reported a significant reduction in the risk of pneumococcal bacteremia but slightly increased risk of hospitalization for pneumonia among the vaccinated. It was similar to our finding that PPV vaccination was associated with a reduced risk of pneumococcal bacteremia but was not associated with a reduced risk of hospitalization for pneumonia; and men vaccinated with PPV in some subgroups were more likely to be hospitalized for pneumonia. The study population was younger (45-69 years old at baseline) and included men only, but with a longer follow-up period (median follow-up was 7.3 years) and might have better controlled for potential confounding factors identified through electronic medical records. The findings in this large cohort of men suggested a benefit of PPV for protection against pneumococcal bacteremia among men vaccinated at age 65 years and older. PPV might not provide adequate protection against all-cause pneumonia hospitalization among men. Additional information is not expected.