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Frostbite causes tissue damage through five major mechanisms, out of which two are amenable to treatment. The first-line treatment is rapid rewarming therapy using water at 40°C to 42°C, which addresses the formation of ice crystals in the intra and extra cellular compartments. The second mechanism is progressive tissue ischemia after rewarming and is only accessible to a second-line therapy represented by thrombolysis. This study aimed to determine the efficacy of thrombolysis. This is a single-center retrospective cohort study, where it was aimed to evaluate two groups of patients. A total of 18 patients were included in this study. Mean times between injury to thrombolytic therapy and admission to thrombolytic therapy was 26.04 hours (SD 13.6) and 9.65 hours (SD 9.89), respectively. All patients suffered injuries ranging from second-degree deep to third degree. The rate of patients having complete, partial, and no angiographic responses were 55.6%, 11.1%, and 33.3%, respectively. The main outcome of interest showed that 11 (61.1%) patients in total had amputations at different levels. Results showed that in the intervention group, five (55.6%) of the patients had amputations compared with six (66.7%) from the control group (P = .6) at comparable levels of amputation. The literature supports that the use of intra-arterial tissue plasminogen activator might be beneficial for severe cases of frostbites; however, it lacks of studies of major significance and results are often controversial. Our study has not shown statistically significant results on amputation levels and cannot support the hypothesis of efficacy of thrombolytic therapy.