This is an open-label, flexible-dose, multicenter study. The study will consist of 3 periods: an up-to-2-week pre-observation (screening) period, an observation period from Day 1 (baseline) to Week 49 (end of observation period) assessment, and a post-observation period from after the Week 49 (end-of-observation period) assessment to Week 57. For the patients who discontinue the study before the last assessment in Week 49, the post observation period will start after the discontinuation from observation period assessment with follow-up visits at 4, 8, and 12 weeks after the last injection. The total duration of the study will be 57 weeks, including the observation and post observation periods. Approximately 200 men and women, aged 20 years or older who meet the DSM-IV-TR criteria for schizophrenia at least 1 year before screening and have a Positive and Negative Syndrome Scale (PANSS) total score of 60 to 120 at screening and baseline will be enrolled, so that at least 100 patients complete this 1-year study. The patients who have a primary active Axis I disorder other than schizophrenia will not be enrolled in the study. Eligible patients will be administered an initial loading dose of paliperidone palmitate 150 mg eq. im on Day 1 and 100 mg eq. 1 week later in the deltoid muscle. The study drug will be administered in a flexible dose range of 25 to 150 mg eq. at 4-week intervals from Week 5 as either deltoid or gluteal muscle injections for a total of 11 injections. A dose of 75 mg eq. is recommended from Week 5 until Week 45. The study drug will be administered by a study drug manager and/or injector. Each dose increase should be in increments of 50 mg eq. or less. Dose increases can be considered if there is an increase in the PANSS total score (individual items or the total) or the Clinical Global Impression - Severity (CGI-S) score from the preceding assessment. Dose decreases can be considered if adverse events occur that appear to have a causal relationship with the investigational drug. The injection site (deltoid or gluteal) will, in principle, be fixed at the fourth injection and thereafter, but injection in the deltoid or gluteal muscle can be alternated at the discretion of the investigator if considered appropriate for the patient's safety. If repeated injections are administered in either the deltoid or gluteal muscles, then alternating the side of each injection (left or right) is recommended. The choice of injection needle will be determined by the patient's weight and by the injection site. The weight at baseline (Day 1) will be used when choosing needles for injection from Day 1 to Week 21, and the weight at Week 25 will be used when choosing needles for injection at Week 25 and thereafter. Patients weighing less than 200 lb (\<90 kg) will receive their deltoid injection with a 1-inch needle (23 G×1"). Patients weighing 200 lb or more (=90 kg), will receive their deltoid injection with a 1.5-inch needle (22 G×1 1/2"). All gluteal injections will be administered with a 1.5-inch needle (22 G×1 1/2"). The sponsor will collect adverse events starting with the signing of the informed consent form until completion of all end-of-study procedures. Adverse events will be followed by the investigator until it recovers or is considered clinically stable. Adverse events include any occurrence that is new in onset or aggravated in severity or frequency from the baseline condition, or abnormal results of diagnostic procedures, including laboratory test abnormalities. Blood samples (preferably fasted), for serum chemistry and hematology and a random urine sample for urinalysis, electrocardiogram (ECG), vital signs, height, weight, waist circumference, Body Mass Index (BMI), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), Columbia-Suicide Severity Rating Scale (C-SSRS), evaluation of the injection site and Visual Analog Scale (VAS) for patient's assessment of injection pain will be also collected for safety evaluation. PANSS total score and CGI-S score will be collected for efficacy evaluation. Samples for pharmacokinetic evaluation will be collected at designated timepoints. An optional 10-mL pharmacogenomic blood sample will be collected from patients who provide a separate written informed consent for this part of the study. The patients will receive paliperidone palmitate intramuscular (im) as an initial loading dose of 150 mg eq. on treatment Day 1 and 100 mg eq. 1 week later in the deltoid muscle. The study drug will be administered in a flexible dose range of 25 to 150 mg eq. at 4-week intervals from Week 5 as either deltoid or gluteal muscle injections for a total of 11 injections. A dose of 75 mg eq. is recommended from Week 5 until Week 45.