The goal of the study was to compare the effect of combination therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), anticytokine therapy with infliximab (IFX), and antibiotic (AB)/immunosuppressive (IS) therapy on the frequency of healing of simple perianal fistulas in Crohn’s disease. Three patient groups were used in our study. The 1st group of patients (age 19 to 58 years, mean 29 years, n = 12) received MSCs culture systemically and locally. The 2nd group of patients with CD (age 20 to 68 years, mean age 36 years, n = 10) received anticytokine therapy with infliximab (IFX). The 3rd group of patients with CD (age 20 to 62 years, mean age 28 years, n = 14) received antibiotics (AB) and immunosuppressors (IS). Treatment effect was assessed by the index of perianal activity of Crohn’s disease (PCDAI) and the frequency of relapses. After 12 weeks, in the 1st group, healing of simple fistulas was noted in 8/12 patients (66.6%), in the 2nd group in 6/10 (60.0%) and in the 3rd group in 1/14 patients (7.1%). After six months, in the 1st group of patients healing of simple fistulas occurred in 8/12 (66.6%), in the 2nd group in 6/10 (60.0%) and in the 3rd group in 1/14 patients (7.1%). After 12 months, in the 1st group, healing of simple fistulas was observed in 7/12 (58.3%), in the 2nd group in 6/10 (60.0%) and in the 3rd group in 2/14 patients (14.3%). After 24 months, among the patients of the 1st group, fistula closure was observed in 5/12 patients (41.6%), in the 2nd group in 4/10 (40.0%) and in the 3rd group in 0/14 patients (0.0%). Combined cellular and anticytokine therapy of CD with perianal lesions significantly contributes to more frequent and prolonged closure of simple fistulas, as compared to antibiotics/immunosuppressors, and to a decrease in the frequency of recurrence of the disease.