BACKGROUND AND AIMS: Ulcerative colitis (UC) is a serious inflammatory bowel disease with significant morbidity and mortality. Infliximab (IFX), a TNF-alpha antagonist, is recommended by the American Gastroenterological Association, but its clinical effectiveness and safety are based on limited studies. This meta-analysis of randomized controlled trials (RCTs) evaluates the efficacy and safety of IFX in moderate-to-severe active UC, providing evidence for its clinical application. METHODS: A systematic search of major English (PubMed, MEDLINE, Web of Science, Embase, Cochrane Library) and Chinese databases (CNKI, SinoMed, Wanfang, VIP) was conducted up to September 25, 2023, to identify RCTs comparing IFX against placebo, aminosalicylates, corticosteroids, or immunosuppressants for moderate-to-severe UC. Pooled analyses assessed short- and long-term clinical response, clinical remission, endoscopic remission (mucosal healing), safety outcomes, and corresponding 95% confidence intervals. Subgroup analyses, heterogeneity assessment, sensitivity analyses, publication bias evaluation (funnel plots), and meta-regression were performed. RESULTS: Twenty RCTs involving 2,350 patients (IFX: n = 1,300; controls: n = 1,050) were included. IFX demonstrated significant superior efficacy versus controls across all primary endpoints: short-term (RR = 1.38, P < 0.001) and long-term clinical response (RR = 1.52, P = 0.007); short-term (RR = 1.38, P < 0.001) and long-term clinical remission (RR = 1.52, P = 0.022); short-term (RR = 1.58, P = 0.001) and long-term endoscopic remission (RR = 1.39, P = 0.010). Adverse event rates did not differ significant between groups (RR = 1.00, P = 0.933). Meta-regression suggested geographical region as a potential source of heterogeneity for short-term clinical response. CONCLUSIONS: IFX has a more positive effect on active UC than placebos, aminosalicylic acid preparations, steroids, or immunosuppressive drugs, but shows no superiority in terms of adverse responses.