Background and Objectives Prospective randomized comparison of intermediate-term outcomes of patients with small renal tumors who were treated with partial nephrectomy (PN) or microwave ablation. Methods Of 102 selected patients with solitary small renal tumors who had prospectively completed at least 2 years of follow-up since December 2004, randomizedly, 54 had either open (19) or laparoscopic (35) PN and 48 had laparoscopic (28) or open (20) microwave ablation. Patient and tumor characteristics, surgical data, complications, histologic and oncologic data, and functional data of the two approaches were compared. Results Patients in microwave ablation group and PN group matched for age, sex, American Society of Anesthesiologists score, body mass index, and tumor size and were respectively followed for median 32 and 36 months. Surgical and hospitalization times were comparable in both groups. Estimated blood loss, complication rates, and decline of postoperative renal function were significantly less in the microwave ablation group (P?=?0.0002, P?=?0.0187, and P?=?0.0092, respectively). The decrease in estimated glomerular filtration rate at the last available follow-up was similar in both groups (P?=?1.0000). There were no disease-specific deaths. KaplanMeier estimates of overall local recurrence-free survival at 3 years were 91.3% for microwave ablation and 96.0% for PN (P?=?0.5414); the respective numbers for renal cell carcinomas were 90.4 and 96.6% (P?=?0.4650). Conclusions Microwave ablation can be also safely and efficiently done for patients with small renal tumors. This intermediate analysis showed that microwave ablation provides favorable results compared to PN. However, longer term data are still needed. J. Surg. Oncol. 2012; 106:316-321. (c) 2012 Wiley Periodicals, Inc.