Renal cryoablation is a minimally invasive, nephron-sparing option that has shown promise in the treatment of patients with solitary small renal lesions suspicious for malignancy. Few large clinical studies have used this promising technology, although intermediate-term data are encouraging. We present a retrospective review and report the outcomes of a large cohort of patients who underwent renal cryotherapy. Patients who were candidates for partial nephrectomy with peripheral lesions ≤5.0 cm in maximum diameter and no history of bleeding disorders were offered cryoablation as definitive therapy. Two freeze–thaw cycles were used for all lesions, and all were characterized by intraoperative ultrasound immediately before freezing. Data were collected as part of standard care, and chart review was performed only in cases of missing data. From February 2001 to March 2005, 85 consecutive patients with an average age of 67 years and a mean tumor size of 2.6 cm (range, 1.2–4.7 cm; median, 2.5 cm), underwent renal cryoablation; 70 procedures were performed laparoscopically. Mean estimated blood loss was 58 mL, with 2 patients requiring transfusion. Mean hospital stay was 3.0 days (range, 0–14 days; median, 2 days) for the entire cohort and 2.2 days (range, 0–7 days; median, 2 days) for the laparoscopic group. A total of 7 laparoscopic cases were converted to an open approach early in the experience, 2 of which were considered technical failures. Mean follow-up was 10 months (range, 3–36 months). Abnormal postoperative enhancement occurred in 2 patients at 3 months and 12 months. Radical nephrectomy in the first revealed no viable tumor; needle biopsy in the second revealed renal cell carcinoma, which prompted nephrectomy. Intraoperative needle biopsy yielded a 59% malignancy rate. We conclude that renal cryotherapy is a viable option for nephron-sparing surgery in small, peripheral renal lesions. The procedure is well tolerated, may be considered in patients who are not good candidates for open surgical approaches, results in minimal morbidity, and has shown encouraging treatment results. Close posttreatment surveillance is essential. Longer-term follow-up data will be necessary if the long-term durability of renal cryotherapy is to be established.