Background: Positioning infliximab (IFX), cyclosporine and tacrolimus (TAC) for treating ulcerative colitis (UC) is in great debate. Methods: A literature search identified studies that investigated IFX vs. cyclosporine or IFX vs TAC in UC patients. Short-term remission, short-term, 1-year and 3-year colectomy rate were employed as primary end-points to assess efficacy. Odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed. Results: Overall, 15 studies comprised 596 patients in IFX group and 866 in calcineurin inhibitors group (644 received cyclosporine and 222 received TAC). No significant difference was seen between IFX and calcineurin inhibitors with regard to short-term remission. IFX led to a lower short-term (OR: 0.59, 95% CI: 0.43-0.82, P:.001), 1-year (OR: 0.53, 95% CI: 0.38-0.73, P < .001), 3-year colectomy (OR: 0.41, 95% CI: 0.20-0.84, P:.02) than calcineurin inhibitors. IFX led to a lower short-term (OR: 0.51, 95% CI: 0.36-0.71, P < .001), 1-year (OR: 0.53, 95% CI: 0.37-0.74, P:.003) colectomy and a trend of lower 3-year colectomy (OR: 0.49, 95% CI: 0.22-1.06, P:.07) than cyclosporine while no significant difference was seen between IFX and TAC. Results of network meta-analysis showed that the order was cyclosporine, TAC and IFX from high rate to low with regard to short-term and 1-year colectomy. Conclusion: IFX treatment leads to a lower short-term, 1-year colectomy rate and a trend of lower 3-year colectomy rate in UC patients than cyclosporine while no significant difference is seen between IFX and TAC. TAC may be superior than cyclosporine with regard to efficacy based on indirect comparisons. Randomized trials with fixed protocol are warranted to identify the optimal medical strategy in patients with UC.