Diabetic nephropathy (DN) is one of the most important causes of the end-stage renal failure and its prevalence is found to be increasing. The presence of hypertension and progressive proteinuria is among the important findings. In this study, the effects of double and triple combinations of trandolapril, telmisartan, and verapamil on proteinuria were investigated in diabetic patients with nephropathy. Seventy-eight patients (mean age: 56.11 11.26 years; 47 females and 31 males) with overt proteinuria and DN were included in this study. The patients were divided into four groups: Group I (n: 18, trandolapril telmisartan), Group II (n: 20, trando- lapril verapamil), Group III (n: 20, trandolapril telmisartan verapamil), and Group IV (n: 20, telmisartan verapamil). At the end of a three-month therapy, within and between group compa- risons were done about the effects of the use of double or triple drug combinations on proteinuria, glomerular filtration rate (GFR), electrolytes, serum albumin, low-density lipoprotein (LDL)- cholesterol, and HbA1C. There was no significant difference among groups in terms of age, gender, diabetes duration, body mass index, and retinopathy frequency. The decreases in protei- nuria and mean arterial blood pressure (MABP) were significant in all groups. The decrease in proteinuria was independent of the decrease in MABP [the reduction rate in proteinuria was 39% (P < 0.001) in Group I, 37% (P < 0.001) in Group II, 42% (P < 0.001) in Group III, and 43% (P < 0.001) in Group IV; the reduction rate in MABP was 10.6% (P < 0.001) in Group I, 13.7% (P < 0.001) in Group II, 17.5% (P < 0.001) in Group III, and 15.4% (P < 0.001) in Group IV]. Decrease in HbA1C (before and after treatment) was significant in Groups III and IV when com- pared to Groups I and II. Any adverse event, like hyperkalemia, was not observed. There was no significant difference among the groups in terms of GFR, LDL-cholesterol, albumin, and potassium. All the patients tolerated the drugs well. In conclusion, in patients with DN, both double or triple combinations of trandolapril, telmisartan and verapamil resulted in signi- ficant decreases in proteinuria and MABP. Triple combinations did not have any supe- riority over double combinations. Therefore, the suitable drug combinations may be chosen according to the clinical status of a patient.