Background and Purpose: American Urological Association guidelines endorse partial nephrectomy as the preferred treatment for patients with small renal masses, while considering patients with significant comorbidities potential candidates for ablative therapy. We compared perioperative, renal functional, and oncologic outcomes of renal cryoablation and robot-assisted partial nephrectomy (RAPN) based on our long-term institutional experience. Patients and Methods: A retrospective review evaluated 267 patients who underwent laparoscopic or percutaneous cryoablation (July 2000-June 2011) and 233 patients who underwent RAPN (June 2007-September 2012) for enhancing renal masses at Washington University. Results: The perioperative complication rate was 8.6% in the cryoablation group vs 9.4% in the RAPN group (P=0.75). There was no significant difference in complication risk between the two treatment modalities on multivariate analysis. Estimated glomerular filtration rate (eGFR) at last follow-up was 6% lower than preoperative eGFR in the cryoablation group and 13% lower in the RAPN group (P<0.01). The advantage of cryoablation in preserving renal function persisted on multivariate analysis (P=0.02). In patients with pathologically proven renal-cell carcinoma, 5-year Kaplan-Meier disease-free survival (DFS), cancer-specific survival (CSS), and overall survival was 83.1%, 96.4%, and 77.1% in the cryoablation cohort vs 100%, 100%, and 91.7% in the RAPN group. Mean time to recurrence was 16.2 months (range 0.03-42.0 mos). Cryoablation was associated with increased recurrence risk (hazard ratio [HR]=11.4, P=0.01) on multivariate analysis. Conclusions: Cryoablation and RAPN are safe alternatives for managing renal masses amenable to nephron-sparing interventions, offering acceptable morbidity and excellent renal preservation. While RAPN offers improved DFS, for those willing to undergo close postoperative monitoring and accept the potential need for re-treatment of recurrent disease, cryoablation offers excellent long-term CSS.