To compare the efficacy and safety of ergocalciferol and calcitriol in stage 3 to 5 chronic kidney disease (CKD) patients, a randomized, prospective, controlled, open-labeled study was designed. 204 patients were enrolled into the present study with following-up duration of 33.2±3.8 months. Patients in Group VitD2 (n=104) and Group aVitD3 (n=100) were treated by ergocalciferol and calcitriol, respectively. The 25-hydroxyvitamin D levels of group VitD2 increased significantly from 15.14±7.46 to 37.32±10.49 ng/ml (P<0.001, t=−19.692) and increased more (P<0.001, t=−14.982) than those of group aVitD3, which increased from 14.90±6.15 to 18.08±7.55 ng/ml. Maintenance target levels of serum calcium, phosphorus, and intact parathyroid hormone as the primary outcome measure did not show significant difference in frequencies between two groups. In summary, treatment of CKD-mineral and bone disorders in CKD patients at stages 3 to 5 using ergocalciferol has a similar long-term efficacy and safety profile as calcitriol.