Objective: To observe the change of clinical indicesontreatment with tacrolimus combined with piperazine ferulate in elderly patients with primary nephrotic syndrome. Methods: Fifty elderly patients with primary nephrotic syndrome were randomly divided into combined therapy group (25 case) and the single therapy group (25 case) to be treated with tacrolimus combined with piperazine ferulate or single tacrolimus for 6 months, respectively. The changes of indices includedserum triglyceride, cholesterol, albumin, creatinine, urea nitrogen, urine protein andtherapeutic efficacy; the two groups were compared. Theadverse reactions were also compared. Results: The overall therapeutic efficacy of combined therapy group and single therapy group were 84% and 72%, respectively (P<0.05). The combined therapy group showed better improvement in serum albumin [(39.9±1.9) g/L vs (34.6±2.1) g/L] and urine protein [(2.5±0.9) g vs (3.6±1.0） g](P<0.05). Adverse reactions showed no significant difference between the combined therapy group and single therapy group（12% vs 8%, P>0.05）. Conclusions: Tacrolimus combined with piperazine ferulate is better than tacrolimus only for the treatment of primary nephrotic syndrome in elderly patients without increase inadverse reactions.