Aim. To determine the efficacy of 0.1% tacrolimus ointment in patients with perianal Crohn’s disease (CD). Subjects and methods. This prospective randomized trial enrolled 20 patients with perianal CD as anal fissures and rectal fistulas. The inclusion criteria were rectovaginal or extrasphincteric fistulas and purulent leakages. A study group comprised 11 patients, including 9 with anal fissures and 2 with fistulas. A control group included 9 patients, including 8 with fissures and 1 with fistulas. The study group received systemic therapy with azathioprine 2 mg/kg/day and tacrolimus ointment 2 mg/day; the control group had systemic therapy with azathioprine 2 mg/kg/day, hormone ointment 1 mg/day, and metronidazole suppositories 250 mg/day. Control examination and perianal CD activity index (PCDAI) determination were done 6 and 12 weeks after therapy initiation. Results. At 6 weeks after beginning the study, local examination revealed the signs of anal fissure epithelialization in 5 (45.5%) of the 11 patients in the study group and in 3 (33.3%) of the 9 patients in the control one. At 12 weeks, fissure epithelialization and fistula obliteration were stated in 6 (54%) patients in the study group and in 3 (33%) of the 9 patients in the control group. At 12 weeks, PCDAI in the study and control groups was 2.00 and 4.44 scores (p=0.01). Conclusion. The findings suggest that topical 0.1% tacrolimus ointment versus antibacterial suppositories and hormone ointments is effective in treating patients with perianal CD. Topical 0.1% tacrolimus ointment therapy caused a reduction in PCDAI.