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BACKGROUND While partial nephrectomy (PN) is considered the standard approach for a tumor in a solitary kidney, percutaneous cryoablation (PCA) is emerging as an alternative nephron-sparing option. OBJECTIVE To compare outcomes between PCA and PN for tumors in a solitary kidney. DESIGN, SETTING, AND PARTICIPANTS Patients who underwent PCA or PN between 2005 and 2015 for a single primary renal tumor in a solitary kidney were identified using Mayo Clinic Registries. Exclusion criteria were inherited tumor syndromes and salvage procedures. INTERVENTION PCA and PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS To achieve balance in baseline characteristics, we used inverse probability of treatment weighting (IPTW) based on propensity to receive treatment. The risk of having a post-treatment complication and percent drop in estimated glomerular filtration rate (eGFR), as well as the risks of local/ipsilateral recurrence, distant metastasis, and cancer-specific mortality, were compared between groups using logistic, linear, and Fine-and-Gray competing risk regression models. RESULTS AND LIMITATIONS The cohort included 118 patients (PCA: 54; PN: 64) with a median follow-up of 47 mo (interquartile range 18, 74). In unadjusted analyses, PCA was associated with a lower risk of complications (15% vs 31%; odds ratio [OR]=0.38; 95% confidence interval [CI] 0.15, 0.96; p=0.04). However, upon accounting for baseline differences with IPTW adjustment, there was no longer a significant difference in the risk of complications (28% vs 29%; OR=0.95; 95% CI 0.53, 1.69; p=0.9). There were no significant differences between PCA and PN in percentage drop in eGFR at discharge (mean: 11% vs 16%; β=-5%; 95% CI -13, 3; p=0.2) or at 3 mo (12% vs 9%; β=3%; 95% CI -3, 10; p=0.3). Likewise, no significant differences were noted in local recurrence (HR=0.87; 95% CI 0.38, 1.98; p=0.7), distant metastases (HR=0.60; 95% CI 0.30, 1.20; p=0.2), or cancer-specific mortality (HR=1.13; 95% CI 0.32, 3.98; p=0.8). Limitations include the sample size, given the relative rarity of renal masses in solitary kidneys. CONCLUSIONS Our study found no significant difference in complications, renal function outcomes, and oncologic outcomes between PN and PCA for patients with a tumor in a solitary kidney. Validation in a larger multi-institutional analysis may be warranted. PATIENT SUMMARY Partial nephrectomy (surgery) and percutaneous cryoablation are both options for treating a kidney tumor while preserving the normal portion of the kidney. In patients with a tumor in their only kidney, we found no difference in the risk of complications, kidney function outcomes, or cancer control outcomes between these two approaches.