OBJECTIVES: To evaluate the risk of hepatotoxicity with the use of nimesulide, a non-steroidal anti-inflammatory drug (NSAID) available in South Korea but withdrawn from the market in several countries. METHODS: A systematic review and meta-analysis was conducted using published studies available at PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the Research Information Sharing Service (a Korean bibliographic database) up to September, 2017. Studies using spontaneous reporting databases were included to estimate reporting odds ratio of hepatotoxicity associated with nimesulide exposure. Collateral references from the selected articles were also manually searched and included in the analysis. RESULTS: A total of 24 studies, including 11 observational studies, 9 single-case reports and 4 case series were evaluated. In a meta-analysis from 5 observational studies while considering hepatotoxicity as a rare outcome, nimesulide was significantly associated with hepatotoxicity (relative risk 2.20, 95% confidence interval (CI) 1.72, 2.81). The sensitivity analysis showed no substantial changes in pooled risk estimates. Based on studies using spontaneous reporting databases (n=5), the reporting of hepatotoxicity was significantly higher in patients using nimesulide compared with the rate in NSAIDs users (pooled reporting odds ratio 5.35, 95% CI 3.68, 7.78). Out of 13 case reports/series with a total of 27 patients, the mean age (± standard deviation) was 57.9 (± 15.9) years and women comprised 85.2% (23 patients). The time course between the exposure of nimesulide and the occurrence of hepatotoxicity ranged from 8 hours to 27 weeks (median 53 days). About one in three patients (33.3%) required liver transplantation or died due to fulminant hepatic failure. CONCLUSIONS: The findings of the meta-analysis supported an increased risk of hepatotoxicity with the use of nimesulide. The present systematic review expands previous knowledge by demonstrating the absolute risk estimates.