While partial nephrectomy remains the gold standard for the management of most small renal masses, increasing experience with renal cryoablation has suggested a viable alternative with a favorable morbidity profile and good efficacy. We report intermediate-term oncologic outcomes from a single-center experience with laparoscopic and percutaneous renal cryoablation. We performed a retrospective review of our laparoscopic renal cryoablation (LRC) and percutaneous renal cryoablation (PRC) experience between January 2003 and April 2007. Patients with at least 12 months of follow-up were included in the analysis. Follow-up consisted of imaging and laboratory studies at regular intervals. Persistent mass enhancement or interval tumor growth was considered a treatment failure. Sixty-six patients (44% women/56% men; 42% African-American/58% Caucasian/other; mean body mass index, 29.7) with 72 tumors underwent either LRC (n = 52) or PRC (n = 20) with a mean follow-up of 30 months (median 25.1 mos; range 13-63 mos). Average patient age was 66.5 years (range 34-82 yrs). Mean tumor size was 2.33 cm (range 1-4.6 cm). Comorbid conditions were prevalent: 76% hypertension, 36% hyperlipidemia, 24% chronic kidney disease, 29% diabetes mellitus, 36% tobacco use, and 32% heart disease. RESULTS of pretreatment biopsy were 62% renal-cell carcinoma and 38% benign or nondiagnostic. Overall cancer-specific and cancer-free survival were 100% and 97%, respectively. There were two treatment failures (3.8%) in the LRC group and five primary failures in the PRC group (25%) (P = 0.015), four of which were salvaged with repeated PRC with no evidence of recurrence at 6 to 36 months of follow-up. There has been no significant local or metastatic progression. LRC and PRC achieved good oncologic control with minimal morbidity at a mean follow-up of 30 months in a patient cohort characterized by numerous comorbid conditions. PRC had a significantly higher primary treatment failure rate than LRC, but re-treatment offered salvage oncologic control with no significant complications.