['Proton pump inhibitors (PPIs) produce negative inotropic effects on the human myocardium at clinically relevant plasma concentrations. We conducted this study to determine whether PPI use was associated with excess mortality in patients with both ischaemic and non-ischaemic heart failure (HF).', 'The impact of PPIs on all-cause mortality was examined using a population-based cohort of Alberta residents over the age of 65 with a diagnosis of HF, logistic regression analysis, and a nested case-control study were used to examine the association between current medication use and mortality. Compared with non-PPI users (n= 15,676, 71% of the HF cohort), PPI users (n= 6431, 29% of the HF cohort) were more likely to be women and had more co-morbidities. Mortality in the first year after diagnosis of HF was 32% (n= 5659) in PPI non-users and 26% (n= 1153) in PPI users. Logistic regression modelling showed that PPI use was associated with a relative reduction in mortality rates compared with non-use [adjusted odds ratio (aOR) = 0.87, 95% confidence interval (CI) 0.81-0.93]. Nested case-control analysis of the 5815 patients who died matched to 9934 controls, revealed that current PPI use was not associated with excess mortality (aOR 0.88, 95%CI 0.77-1.01), while use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker s (aOR 0.70, 95%CI 0.62-0.79) or beta-blockers (aOR 0.57, 95%CI 0.50-0.66), was associated with a relative reduction in mortality.'] Is use of oral proton pump inhibitors associated with harm in patients with chronic heart failure in an ambulatory setting?