The management of patients with steroid-dependent nephrotic syndrome (SDNS) refractory to treatment with long-term steroids, levamisole and cyclophosphamide is difficult. We report our experience on long-term treatment with mycophenolate mofetil (MMF) and alternate-day prednisolone in 42 patients with SDNS previously treated with levamisole (n = 35) and/or cyclophosphamide (n = 37). The mean age (range) at onset of nephrotic syndrome was 37 (13-92) months and at treatment with MMF 104.7 (32-187) months. MMF was administered at a mean daily dose of 26.5 (16.6-31.3) mg/kg for 14.3 (6-45) months. The mean 6-monthly relapse rates decreased from 3.0 episodes before therapy to 0.9 episodes in the first 6 months, 0.7 in next 6 months, and 0.3 in those treated longer than 12 months (P < 0.0001). While on therapy, 32 (76.2%) patients showed 50% or more reduction in relapse rates, and nine (21.4%) had sustained remission. The cumulative dose of prednisolone declined significantly from 0.6 mg/kg per day before to 0.3 mg/kg per day while receiving MMF. Prednisolone requirement was reduced by 50% or more in 16 patients and between 40% and 50% in eight patients. Treatment continuation beyond 12 months resulted in sustained steroid sparing and reduced need for alternative treatments while maintaining low relapse rates. No patients had diarrhea, hematological abnormalities, or impaired renal function. This data confirms the efficacy and safety of treatment with MMF and tapering doses of alternate-day prednisolone in patients with SDNS and supports its use for longer than 12 months.