OBJECTIVES: The current study aimed at assessing the impact of LAIs versus OAs on hospitalizations among patients with schizophrenia by conducting a thorough systematic review of studies with different study designs and performing a meta-analysis. METHODS: Using the PubMed database and major psychiatric conference proceedings, a systematic literature review for 01/2000–07/2013 was performed to identify English-language studies evaluating schizophrenia patients treated with atypical antipsychotics. Studies reporting hospitalization rates as a percentage of patients hospitalized or as the number of hospitalizations per-person per-year were selected. A meta-analysis of the percentage decrease in hospitalization rates from baseline during treatment was conducted as a primary analysis. The secondary analysis was a meta-analysis of the absolute rate of hospitalization during follow-up. Pooled treatment-effect estimates were calculated using random-effect models. To account for differences in patient and study-level characteristics between studies, meta-regression analyses were used. Subset analyses further explored the heterogeneity across study designs. No adjustment was made for multiplicity. RESULTS: Fifty-eight studies evaluating 25 arms (LAIs: 13 arms, 4,516 patients; OAs: 12 arms, 23,516 patients) in the primary analysis and 78 arms (LAIs: 12 arms, 4,481 patients; OAs: 66 arms, 96,230 patients) in the secondary analysis were identified. Reduction in hospitalization rates for LAIs was 20.7 percentage points higher than that of OAs (random-effect estimates: LAIs=56.2% vs OAs=35.5%, P=0.023). Controlling for patient and study characteristics, the adjusted percentage reduction in hospitalization rates for LAIs was 26.4 percentage points higher than for OAs (95%CI: 3.3-49.5, P=0.027). As for the secondary analysis, no significant difference between LAIs and OAs was observed (random-effect estimate: -8.6, 95%CI: -18.1-1.0, P=0.077). Subset analyses across type of study yielded consistent results. CONCLUSIONS: Results of this meta-analysis including studies with both interventional and non-interventional designs and using meta-regressions, suggest that LAIs significantly reduce hospitalization rates for schizophrenia patients compared to OAs.