OBJECTIVE To characterize population-based practice patterns, disease-specific and overall mortality, and cost associated with salvage cryotherapy (SCT) vs salvage radical prostatectomy (SRP). METHODS We retrospectively identified 440 men who failed primary radiation therapy and subsequently underwent SCT (n = 341, 77.5%) or SRP (n = 99, 22.5%) between 1992 and 2009 from Surveillance, Epidemiology, and End Results-Medicare linked data. Propensity score analyses were used to compare overall and prostate cancer-specific mortality and associated Medicare expenditures for SRP vs SCT. RESULTS Men undergoing SCT were more likely to be white (P <.001), less likely to be high school graduates (P = .008), and experienced shorter median time from diagnosis to salvage therapy (44.1 vs 60.1, P <.001) and from primary radiotherapy to salvage therapy (38.7 vs 55.8 months, P <.001). In adjusted analyses, overall mortality was higher (21.6 vs 6.1 deaths/100 person years, P <.001) for SRP vs SCT. There was a trend for higher prostate cancer-specific death rates with SRP vs SCT (6.5 vs 1.4 deaths/100 person years, P = .061). Medicare expenditures for SRP vs SCT were more than 2-fold higher ($19,543 vs $8,088, P <.001). CONCLUSION SRP vs SCT is associated with higher overall mortality and greater health care expenditures. However, longer follow-up is needed to assess long-term functional outcomes and cancer control. UROLOGY 83: 653-657, 2014. (C) 2014 Elsevier Inc.