OBJECTIVES: While several randomized controlled trials (RCTs) have been conducted to assess lurasidone and brexpiprazole for the acute treatment of patients with schizophrenia, head-to-head trial data do not exist. This network meta-analysis indirectly compared the efficacy and tolerability of lurasidone with brexpiprazole.  METHODS: Systematic literature review identified 8 RCTs (5 for lurasidone and 3 for brexpiprazole for the acute treatment of schizophrenia), which were compared using a Bayesian network meta-analysis. Efficacy and tolerability outcomes included Positive and Negative Syndrome Scale (PANSS) change from baseline, Clinical Global Impressions severity score (CGI-S) change from baseline, weight change from baseline, and ≥7 % weight gain at 6 weeks. Fixed-effects and random-effects models were conducted. Median differences were calculated for PANSS, CGI-S and weight change from baseline, and odds ratio (OR) was calculated for ≥7 % weight gain; 95% credible intervals (CrI) were reported.  RESULTS: Similar results were found between fixed-effects and random-effects models. Using a random-effects model, lurasidone was associated with comparable median changes for PANSS (-2.49, 95% CrI: -8.73, 3.86), CGI-S (-0.15, 95% CrI: -0.57, 0.28), and weight change from baseline (-0.69, 95% CrI: -1.42, 0.03), respectively, versus brexpiprazole. The trend showed that lurasidone patients were half as likely to experience ≥7 % weight gain at 6 weeks compared to brexpiprazole patients (OR=0.49, 95% CrI= 0.11, 2.29), although not statistically significant.  CONCLUSIONS: Lurasidone was found to have comparable efficacy and tolerability, with the trends showing favorable efficacy and less weight gain, compared to brexpiprazole in this network meta-analysis.