: This cohort study aimed to elucidate the real-world treatment course of patients receiving low-dose olanzapine (<2.5 mg), to assess its efficacy, and to examine its metabolic side effects. This study was a cohort study using a clinical registry. : The primary efficacy endpoint was effective medication adherence and appropriate dosing. The primary safety endpoint was the incidence of metabolic adverse events, including diabetes mellitus, dyslipidemia, cardiovascular events, and cerebrovascular events. Cox proportional hazards models were used to compare outcomes between groups. : A total of 9565 patients were prescribed olanzapine at Samsung Medical Center from 2002 to 2023, and 1629 (17%) were in the low-dose group. The median maintenance period for low-dose olanzapine was 142 days (IQR, 30-551 days), and 95.5% of patients received low-dose olanzapine with either gradual tapering or gradual dose escalation. During follow-up, the risk of diabetes mellitus (HR = 0.32, 95% CI = 0.17-0.62), dyslipidemia (HR = 0.59, 95% CI = 0.42-0.82), cardiovascular disease (HR = 0.88, 95% CI = 0.51-1.49), and cerebrovascular events (HR = 0.75, 95% CI = 0.41-1.36) was lower in the low-dose group than in the regular-dose group. : Low doses of olanzapine have clinical benefits in providing appropriate dosing and a reduced incidence of metabolic side effects. These findings support personalized antipsychotic treatment strategies, particularly in populations with heightened metabolic vulnerability, by informing dose selection based on individual risk-benefit profiles.