Background: The efficacy of stent-assisted endovascular therapy (EVT) in patients with critical limb ischemia (CLI) compared to bypass surgery (BSX) remains unclear. Methods and Results: This study was performed as a multicenter retrospective registry. Between January 2004 and December 2009, 460 CLI patients (460 first treated limbs) who underwent BSX (237 patients) or EVT (223 patients) for de novo infrainguinal lesions were identified retrospectively and analyzed. The main endpoints of this study were amputation-free survival (AFS), overall survival, limb salvage rate and freedom from major adverse limb events (MALE; includes any repeat revascularization and major amputation). Three-year AFS, limb salvage rate and overall survival were not different between the BSX and EVT groups (60.3% vs. 58.0%, P=0.43; 85.1% vs. 84.2%, P=0.91; 67.2% vs. 69.8%, P=0.96, respectively), but freedom from MALE was significantly lower in the EVT group during follow-up (69.1% vs. 51.1%, P=0.002). After adjusting endpoints with covariates, there was also no significant difference in AFS, limb salvage, and overall survival between EVT and BSX. Freedom from MALE, however, was still significantly lower in the EVT group (hazard ratio, 0.66; 95% confidence interval: 0.47–0.92, adjusted P=0.01). Conclusions: Serious adverse events with the exception of MALE after EVT seem to be acceptable compared to that after BSX in patients with CLI due to infrainguinal disease.  (Circ J 2013; 77: 2102–2109)