This study aimed to investigate the efficacy of Yan-Shen capsule, a traditional Chinese medicine compound, on patients with advanced chronic kidney disease (CKD). A randomized prospective clinical trial was conducted to investigate the efficacy of Yan-Shen capsule on hospital patients with advanced CKD (stages III to IV). Each group included 82 patients (males and females), and all patients were followed up every month for three years. From the Yan-Shen capsule group, 13 patients (16%) reached the endpoints of the study, 64 (78%) continued at stage IV or below, and 5 were not followed up. From the Niao-Du-Qing granules group, 18 patients (22%) reached the endpoints, 60 (73%) continued at stage IV or below, and 4 were not followed up. From the placebo group, 46 patients (56%) reached the endpoints, 30 (37%) continued at stage IV, and 6 were not followed up. As for the patients who reached the endpoints, a significant difference existed between the Yan-Shen capsule group and the placebo group (P < 0.05), but no significant difference was observed between the Yan-Shen capsule group and the Niao-Du-Qing granules group (P > 0.05). Annual serum creatinine (SCr) increase, glomerular filtration rate (GFR) decrease, and erythropoietin requirement of the Yan-Shen capsule group were much lower than those of the placebo or Niao-Du-Qing granules group. Both Yan-Shen capsule and Niao-Du-Qing granules had significant protective effects on residual renal function in advanced CKD and were able to delay the progression to dialysis without obvious side effects. Yan-Shen capsule may be superior to Niao-Du-Qing granules in terms of protecting residual renal function and modifying anaemia.