Abstract: We report three cases of metastatic renal cell carcinoma (RCC) in which combination treatment of cimetidine, cyclooxygenase-2 inhibitor and renin-angiotensin system inhibitor (angiotensin converting enzyme inhibitor or angiotensin II type 1 receptor antagonist) (CCA therapy) was effective. Case 1: A 47-year-old man who had a 12-cm right renal tumor with multiple pulmonary and hepatic metastases refused cytokine therapy for economic reasons and received CCA therapy. All of the metastases showed partial remission, which continued for 12 months. Case 2: A 62-year-old man with multiple pulmonary and mediastinal lymph node metastases from clear cell RCC refractory to interferon-α and interleukin-2 started CCA therapy. Partial remission has been maintained for 16 months. Case 3: A 64-year-old man with pulmonary metastases from clear cell RCC discontinued interferon-α treatment due to its side effects after six months and received CCA therapy. Pulmonary metastases showed partial remission for 31 months. The CCA therapy could be an alternative treatment for metastatic RCC patients unfit for cytokine therapy.