OBJECTIVE Fecal microbiota transplantation (FMT) has been found to be a potential treatment for Crohn's disease (CD). We sought to perform a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD. METHODS Electronic databases were searched for studies until January 2023. Clinical remission was established as the primary outcome. The secondary outcome was clinical response, endoscopic remission, minor adverse events, serious adverse events, and changes in disease activity indices, biochemical indicators, and microbial diversities. Pooled effect sizes and 95% confidence intervals (CIs) were calculated under the random effects model. RESULTS Eleven cohort studies and one randomized controlled trial involving 228 patients were included. In a meta-analysis, the pooled proportion of adult patients with active CD that achieved clinical remission 2 to 4 weeks after FMT was 57% (95% CI = 49-64%) with a low risk of heterogeneity (I2 = 37%). Furthermore, our results showed that FMT significantly (standardized mean difference = -0.66; 95% CI = -1.12 to -0.20; I2 = 0) reduced Crohn's disease activity index scores 4 to 8 weeks after FMT. Subgroup analyses showed no difference between FMT methodologies, except for pre-FMT treatment with antibiotics (P = 0.02). Most adverse events were self-limiting and disappeared spontaneously within hours or days after FMT. Microbiota analysis showed an increased Shannon diversity and a shift toward donor-like microbiome after FMT. CONCLUSIONS FMT could be a promising therapy in the short-term treatment of active CD. More placebo-controlled randomized trials with a long-term follow-up treatment are necessary. BACKGROUND https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322694 No. CRD42022322694.