Background: Pouchitis and secondary Crohn's disease (CD)-like complication of the pouch are the most common complications after ileal pouch-anal anastomosis following colectomy for ulcerative colitis. Data about the effectiveness of anti-TNF agents in these two entities remains sparse. We aimed to perform a systematic review and meta-analysis to evaluate the efficacy of anti-TNF therapy in differentiating patients with chronic refractory pouchitis and CD-like complications. Methods: Systematic literature search was performed in MEDLINE and from international meetings abstracts. The search process, selection of manuscripts, and data extraction were performed independently by two physicians according to PRISMA statements. Prevalence and 95% confidence interval (CI) were estimated using random-effects models assuming between and within study variability. Statistical heterogeneity between results was assessed by examining forest plots, CIand using I2 and sensitivity analyses were conducted. CD-like complications of the pouch were defined as the presence of non-anastomotic fistula and/or non-anastomotic stenosis and/or prepouch ileitis. Chronic refractory pouchitis was defined as inflammation limited to the pouch. The short term and the long term responses were evaluated at 8 weeks and 12 months, respectively. Results: We identified 21 articles and three abstracts including 313 patients treated either with infliximab (IFX) (n=194) or adalimumab (ADA) (n=119) for inflammatory complications of the pouch. The rate of complete response (CR) after anti-TNF induction therapy for inflammatory complications of the pouch was 0.51 (95% CI [0.39–0.64]; I2=0.56). The rate of short-term CR was 0.57 (95% CI [0.38–0.75]; I2=0.36) for IFX-treated patients compared to 0.38 (95% CI [0.08–0.72]; I2=0.50) for ADA-treated patients (p=0.20). The long-term rate of CR in patients treated with anti-TNF therapy was 0.52 (95% CI [0.39–0.65]; I2=0.59), with 0.59 (95% CI [0.45–0.72]; I2=0.30) for IFX-treated patients compared to 0.30 (95% CI [0.15–0.46]; I2=0.00) for ADA-treated patients (p=0.19). The rate of CR after anti-TNF induction therapy seemed to be higher for CD-like complications of the pouch 0.64 (95% CI [0.5–0.77]; I2=0.18), compared to refractory pouchitis 0.10 (95% CI [0.08–0.35]; I2=0.00) (p=0.06). The rate of long-term CR in patients treated with anti-TNF was 0.57 (95% CI [0.43–0.71]; I2=0.32) for CD-like complications of the pouch compared to refractory pouchitis 0.37 (95% CI [0.14–0.62]; I2=0.47) (p=0.57). Conclusions: Despite wide heterogeneity of the data, anti-TNF agents have a clear trend to have higher and faster efficacy in CD-like complications of the pouch compared to refractory pouchitis, highlighting the need to differentiate these two entities in clinical practice.