BACKGROUND: Vascular thrombosis secondary to frostbite can lead to ischemic tissue damage in severe cases. Threatened extremities may be salvaged with thrombolytics to restore perfusion; however, current data are limited to single institution case series. The authors performed a systematic review to determine the efficacy of thrombolytic therapy in treating upper extremity frostbite. METHODS: PubMed, EBSCO, and Google Scholar were queried using the keywords "thrombolytics," "frostbite," "fibrinolytics," and "tPA." Exclusion criteria were failure to delineate anatomic parts injured, failure to report number of limbs salvaged, animal studies, and non-English language publications. Thrombolytic therapy was defined as intraarterial (IA) or intravenous (IV) administration of tissue plasminogen activator (tPA), alteplase, urokinase, streptokinase, or any tPA derivative. RESULTS: A total of 42 studies were identified, with 13 satisfying inclusion criteria. Eight studies reported catheter-directed IA thrombolysis, four reported systemic IV administration, and 1 reported both methods. A total of 157 patients received thrombolytics. In all, 73 upper extremity digits were treated by IA route and 136 digits were treated by IV route. Overall upper extremity digit salvage rate was 59%. There was a significantly higher salvage rate in digits treated by the IA route compared to the IV route. CONCLUSIONS: Thrombolytics, particularly when administered by the intra-arterial route, are emerging as a promising treatment of severe frostbite of the upper extremity, increasing digit salvage rates.