OBJECTIVES: The objective of this study was to compare the efficacy, complications, and costs associated with urokinase versus alteplase for the catheter-directed treatment of acute peripheral artery disease (APAD). METHODS: The cost-effectiveness of catheter directed thrombolysis (CDT) with urokinase and alteplase for the treatment of APAD was compared using decision analysis. A literature-based decision model to evaluate cost-effectiveness was constructed. Successful treatment outcomes were defined as clot lysis with a subsequent 30-day survival posttreatment. Direct medical costs were assessed from the payer perspective in the Kazakhstan and analyzed using sensitivity analyses. A Monte Carlo analysis with 1000 patients was performed to obtain mean and incremental cost-effectiveness ratios (ICERs). RESULTS: The mean cost-effectiveness ratio was $148 463 per treatment success for CDT with urokinase  and  $220 052 for CDT with alteplase. The ICER for  alteplase relative to  urokinase was $211 573 per additional CDT treatment success. Approximately 75% of simulated cases indicated that alteplase was associated with increased costs and increased treatment success compared with urokinase. Also, when using alteplase higher risk of bleeding than with urokinase, this complication is a major factor limiting the using of СDT. Results of a post hoc sensitivity analysis indicated that dominance decreased to approximately 10% of cases only under the most strict criteria. CONCLUSIONS: Decision analysis found an ICER of $211 573 per additional CDT treatment success for alteplase relative to urokinase in the treatment of APAD from the perspective of the payer in the Kazakhstan. In about 75% of cases resulting from a Monte Carlo simulation, alteplase was associated with increased costs and slightly increased CDT treatment success compared with urokinase, although this finding was sensitive to the distributional assumptions made concerning certain costs in the model.