Mesenchymal stromal cells (MSCs), which have immunomodulatory properties and a large regenerative potential, are now used to treat fistula in Crohn's disease (CD). Aim: compare the effectiveness of combined therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), infliximab (IFX) and antibiotics (AB)/immunosuppressors (IS) on the frequency of healing of simple perianal fistulas in CD. 50 patients with CD were divided into four groups, depending on the method of therapy. The first group of patients (n = 12) received MSCs systemically and locally according to the scheme. The second group (n = 10) received therapy of IFX according to the scheme. The third group (n = 14) received AB and IS. The fourth group (n = 14) received IFX according to the scheme and local MSCs. In the dynamics the closure of the external fistula opening was evaluated at 12, 26, 52 and 104 weeks from the start of therapy. After 12 weeks among patients of the first group, healing of simple fistulas was noted in 10/12 patients (83.3%), in the second group, healing of simple fistulas was noted in 8/10 (80.0%) (RR-0.83; 95% CI 0.14–4.9, p = 0.72). In the third group, healing of simple fistulas was noted in 5/14 patients (35.7%) (RR-0.26, 95% CI 0.07–0.97, p = 0.04 compared with the first group). In the fourth group, healing of simple fistulas was noted in 13/14 patients (92.8%) (RR −0.90, 95% CI 0.67–1.2, p = 0.88 in comparison with the first group). After 26 weeks in the first group, healing of simple fistulas was preserved in 8/12 (66.6%) patients, and in the second group it was preserved in 7/10 (70.0%) patients (RR −1.11, 95% CI 0.32–3.84, p = 0.76). In the third group, in 4/14 patients (28.6%) (RR −0.47, 95% CI 0.2–1.11, p = 0.12 compared with the first group). In the fourth group, 13/14 patients (92.8%) (RR −0.72, 95% CI 0.47–1.1, p = 0.23). After 52 weeks in the first group, the healing of simple fistulas was preserved in 7/12 (58.3%), and in the second group it was preserved in 6/10 (60.0%) (RR −1.25, 95% CI 0.48–3.22, p = 0.69). In the third group, in 2/14 patients (14.3%) (RR −0.49, 95% CI 0.24–0.98, p = 0.03 compared with the first group). In the fourth group, 13/14 patients (92.8%) (RR-0.63, 95% CI 0.38–1.04, p = 0.1). In 104 weeks, among the patients of the first group, fistula closure was maintained in 5/12 patients (41.6%), in the second group in 5/10 (50.0%) (RR −1.17, 95% CI 0.53–2.55, p = 0.96). In the third group, in 0/14 patients (0.0%) (RR-0.58, 95% CI 0.36–0.94, p = 0.01 compared with the first group). In the fourth group, 13/14 patients (92.8%) (RR-0.45, 95% CI 0.23–0.89, p = 0.016 in comparison with first group; RR-0, 54, 95% CI 0.28–1.00, p = 0.05 in comparison with the second group). Combination anti-cytokine therapy and local mesenchymal stromal cells therapy contribute to the more frequent and prolonged closure of simple fistulas in patients with CD in comparison with other known therapy.