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Introduction: Technological advancements have reduced the morbidity associated with cryosurgery, leading to an increased interest in this modality for the treatment of organ-confined prostate cancer. In this study, we critically examine the current role of cryoablation of the prostate to better understand how to counsel patients regarding this treatment option., Methods: A database was compiled over a 3-year period (2008-2011) of 30 patients who underwent cryoablation for organ-confined prostate cancer. Indications for cryosurgery included primary treatment, focal treatment (institutional review board-approved prospective study), and salvage cryotherapy for radiation failure. The primary outcomes were biochemical response via prostate-specific antigen (PSA) measurement and morbidity associated with cryoablation. Cryotherapy failure was defined as an increasing postcryotherapy PSA level ≥ 2 ng/mL above the post-treatment nadir, a positive prostate biopsy, or radiographic evidence of metastatic disease., Results: Of the 30 patients who underwent cryoablation from 2008 to 2011, 26 patients had complete follow-up data for analysis. Of these patients, 17 (65.38%) had total gland cryotherapy, 5 (19.23%) had salvage cryotherapy for radiation failure, and 4 (15.38%) had focal cryotherapy. The mean patient age was 68 years (54-89); median preoperative PSA was 5.5 ng/mL (1.7-15.9); median prostate volume was 35 mL (15-54); mean Gleason score was 7; and the median PSA at study conclusion was 0.7 (0.02-3.4) ng/mL. Of the 17 patients who had total prostate cryotherapy, 11 (64.7%) had significant factors precluding primary treatment by a surgical and/or radiation approach, including neurological disorders (2), morbid obesity (1), rectal cancer treated with radiation (1), kidney/pancreas transplant (2), ileoanal pouch secondary to inflammatory bowel disease (IBD) (1), renal failure (1), and age (3). There were no intra- or postoperative complications. After a median follow-up of 18 months (1-40), none of the patients with multiple comorbidities had biochemical failures. Two patients from the salvage group experienced treatment failure requiring androgen deprivation therapy., Conclusions: This critical analysis of a single-surgeon experience at a large academic prostate cancer program revealed that the contemporary role of cryosurgery is, in select patients with comorbidities, preventing surgical and/or radiation therapy. Additionally, cryosurgery has a role in treating radiation failures. Further studies are necessary to investigate focal cryotherapy as an option for primary treatment, but our preliminary results are promising, without any biochemical failures in our focal therapy cohort.