In order to determine the long-term effects of cyclophosphamide (CPO) and to identify parameters associated with sustained remission, we retrospectively studied the data from 90 patients with steroid-dependent nephrotic syndrome (SDNS) who received a single course of oral cyclophosphamide (2 mg/kg/day for 10 to 12 weeks). The median follow-up period after CPO was 5.5 years (interquartile range 3.2-8.5). Sustained remission reached the cumulative rate of 57% at 1 year, 42% at 2 years, and 31% at 5 years. For the patients who relapsed, the median threshold dose of prednisone between CPO initiation and first relapse has significantly decreased (22.1 mg/kg/day versus 4.9 mg/kg/day, p < 0.001). No further immunosuppressive agent was required in 60% of all patients. Young age at CPO initiation was associated with a lower rate of sustained remission (p < 0.001). Age at diagnosis of nephrotic syndrome, gender, cumulative dose of CPO (in mg/kg), and level of steroid dependence at CPO initiation did not influence the outcome. The incidence of side effects was low. These findings suggest that despite the wide use of new immunosuppressive agents, a short course of CPO remains an effective second-line therapy in SDNS patients. Optimal efficiency was observed in children over 7.5 years.