OBJECTIVE: We investigated the efficacy and safety of tacrolimus in patients with primary focal segmental glomerulosclerosis (FSGS) resistant to treatment in this study. MATERIAL and METHODS: This prospective study included 9 patients (5 female/4 male) with FSGS resistant to steroids. Their immunosuppressive treatments except corticosteroids were stopped at least six months previously. Tacrolimus (4 mg/day) treatment was administered. The daily urinary protein excretion, serum creatinine, albumin and total cholesterol values were measured before and after treatment. RESULTS: The mean level of daily urinary protein excretion, serum creatinine and serum albumin at the baseline was 4.7 ± 3.3 g/day, 1.2 ± 0.6 mg/dL, and 3.5 ± 0.7 g/dL, respectively. The daily urinary protein excretion significantly reduced from the 1st month of the treatment. At the 6th month, complete remission was achieved in 3 patients (33%) and partial remission in 2 patients (22%). 3 patients were resistant to the treatment. There was no difference in serum albumin, creatinine and cholesterol levels after the treatment when compared to the baseline levels. CONCLUSION: Tacrolimus is a safe and effective treatment in patients with FSGS resistant to treatment. However, the tendency to relapse in all patients who have complete or partial remission when the treatment was withdrawn demonstrates dependence on treatment.