Summary Background The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required. Aim To review systematically the literature to assess fistula healing rates with medical treatment (anti‐TNF‐α therapies ± immunomodulators) or surgical treatment alone, compared with combined medical and surgical treatment in fistulising perianal Crohn's disease (CD). Methods The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were used. Two independent reviewers searched the literature. Results Twenty‐four articles were included. The total population was 1139 patients; 460 (40%) received single treatment with either medical or surgical therapy, and 679 (60%) received combined medical and surgical therapy. Eight studies compared single and combination therapy, with a total population of 797 patients (single therapy: n = 448, combination therapy: n = 349). In the single therapy group, 191/448 were in complete remission (43%). This was lower than the healing rate of the combination therapy group 180/349 (52%). No response to therapy was noted in 34% (153/448) of the single therapy group compared with 23% (80/349) of the combination group. Conclusions Combined surgical and medical (anti‐TNF‐α ± immunomodulators) therapy may have additional beneficial effects on perianal fistula healing in patients with Crohn's disease, compared with surgery or medical therapy alone. A well‐designed Crohn's perianal fistula clinical trial is required in a multidisciplinary medical and surgical setting, with clearly defined end points of clinical (and likely patient reported outcomes) and radiological healing.