5-Hydroxytryptamine type 2 antagonists are used to treat symptomatic peripheral arterial disease. However, it remains unknown as to whether the administration of sarpogrelate, a 5-hydroxytryptamine type 2 antagonist, improves the prognosis after endovascular therapy for critical limb ischemia (CLI). We performed a retrospective analysis using a database of 386 Japanese patients undergoing endovascular therapy for CLI. Sixty-seven patients were treated with sarpogrelate, and we compared their prognosis with that of an equal number of background-matched controls extracted from the population. The primary end point was the first event of either major amputation or death from any cause, and amputation-free survival was evaluated. The follow-up period was 21 ± 18 months (mean ± standard deviation), and 58 end points were observed. Patients treated with sarpogrelate had a significantly higher amputation-free survival rate than their matched controls (P = 0.036). The hazard ratio for the end point and its 95 % confidence interval was 0.57 (0.34-0.97). These results suggest that sarpogrelate treatment is associated with a favorable prognostic outcome in CLI patients undergoing endovascular therapy. Future prospective studies are required to investigate whether sarpogrelate treatment would improve the prognosis of CLI patients.