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Retrograde infrageniculate access is an alternative treatment strategy for patients who have failed to respond to antegrade endovascular intervention. This study compares the outcomes of infrageniculate retrograde arterial access with the conventional transfemoral access for the endovascular management of chronic lower extremity ischemia.This was a retrospective single-center review of retrograde endovascular intervention (REI) from 2012 to 2016. Indications for intervention, comorbidities, complications, procedural success, limb outcomes, and mortality were analyzed. Technical failure was defined as the inability to complete the procedure because of failed access or unsuccessful recanalization. Infrageniculate access and transfemoral access were obtained with ultrasound or angiographic roadmap guidance. Patency rates were calculated for technically successful interventions.There were 47 patients (85% presenting with critical limb ischemia) who underwent sheathless REI after failed antegrade recanalization of TransAtlantic Inter-Society Consensus class D infrainguinal lesions, whereas 93 patients (83% with critical limb ischemia) underwent standard transfemoral access. There were 16 (34%) femoropopliteal, 14 (30%) tibial, and 17 (36%) multilevel interventions in the retrograde group compared with 41 (41%) femoropopliteal, 20 (20%) tibial, and 39 (39%) multilevel interventions in the transfemoral group. Access sites for the retrograde group included the dorsalis pedis (26%), midcalf peroneal (24%), anterior tibial (22%), posterior tibial (26%), and popliteal (2%) arteries. Overall technical success was achieved in 57% of the retrograde group compared with 78% of the transfemoral group. Mean follow-up was 20 months (range, 1-45 months). There were no significant differences in the primary patency rates between the two groups at 1 year and 2 years. The primary assisted patency rates were significantly better in the transfemoral group at 1 year (66% vs 46%; P = .031) and 2 years (56% vs 29%; P = .031). The secondary patency rates were higher in the transfemoral group at 1 year (93% vs 83%; P = .079) and 2 years (91% vs 76%; P = .079), although this did not reach statistical significance. The rate of reintervention was 41% for the retrograde group vs 40% for the transfemoral group. Most of the reinterventions (70% in the retrograde group and 61% in the transfemoral group) were endovascular interventions for a restenosis or occlusion.Infrageniculate access for REI can result in primary patency rates similar to those of antegrade interventions and does not compromise the access site. Technical failure is high in this initial experience and is mostly due to failed recanalization. Limb salvage may be achieved after technical failure with either repeated antegrade intervention or surgical bypass.