Abstract Background The management of patients with fistulising Crohn’s disease (CD) is challenging. Several biologics have been used for the treatment of fistulising CD over the last two decades. We aimed to compare the efficacy of biologic therapies in inducing response and remission in fistulising Crohn’s disease. Methods Systematic searches were made of MEDLINE, EMBASE, Scopus, Cochrane Central databases for randomized controlled trials (RCTs) to November 2021 that assessed the efficacy of infliximab, adalimumab, certolizumab, vedolizumab, or ustekinumab against placebo or an active agent for induction of response or remission in adult Crohn’s patients with fistulising disease. Primary outcome was proportion of patients with fistula response or remission as defined by each RCT. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% confidence interval (CI). Results Ten studies were included in the analysis. Main analysis showed that there was no statistical difference in inducting remission between infliximab, adalimumab, certolizumab, vedolizumab and ustekinumab. Anti-TNFs were superior to placebo in inducing response [OR= 0.51 (95% CI 0.35; 0.750] and remission [OR= 0.36 (95% CI 0.22; 0.58)]. Infliximab was superior to placebo in inducing response [OR= 0.36 (95% CI 0.17; 0.75)] and remission [OR=0.17 (95% CI 0.03; 0.87)]. Ustekinumab was superior to placebo in inducing response [OR=0.48 (95% CI 0.26; 0.860] but not remission [OR=0.50 (95% CI 0.13; 1.93)]. Vedolizumab was not superior to placebo in inducting remission [OR=0.32 (95% CI 0.04; 2.29)]. Certolizumab was not superior to placebo in inducting response [OR=0.78 (95% CI 0.40; 1.55)] or remission [OR= 0.78 (95% CI 0.40; 1.55)]. Infliximab was superior to adalimumab in inducting response [OR=0.24 (95% CI 0.06; 0.99)] but not remission [OR=0.31 (95% CI 0.04; 2.27)]. Conclusion In patients with fistulising Crohn’s disease, anti-TNFs are effective in inducing response and remission. Infliximab was superior to adalimumab in inducing response but not remission. No difference among various biologics was observed for inducing remission. These data highlight the need for dedicated studies to assess the efficacy of biologics in fistulising Crohn’s disease.