Background: The concomitant use of femoral and popliteal accesses has been recommended for challenging superficial femoral artery (SFA) occlusions, but no comprehensive comparison of this approach to a strategy of femoral access only is available. We thus aimed to appraise the risk-benefit balance of retrograde popliteal access as bail-out strategy for SFA occlusions. Methods: Consecutive patients with symptomatic SFA occlusion and undergoing percutaneous revascularization were enrolled. We distinguished patients in whom retrograde popliteal access was required as bail-out strategy versus those not requiring such access. The primary end-point was procedural success. Results: A total of 130 patients (152 limbs) were included, with 23 patients (25 limbs) requiring retrograde popliteal access. Occlusion length was 20.6 ± 8.8 cm in those requiring popliteal access versus 18.5 ± 8.5 cm in those without popliteal access, with TASC C/D lesions in 23 (92%) versus 106 (83%). Procedural success was achieved in 92 out of 107 patients (86.0%) treated with a standard approach and 22 out of 23 patients (95.7%) treated with retrograde popliteal access (total 114 out of 130 [87.7%]) and 112 out of 127 limbs (88.2%) and 24 out of 25 limbs (96.0%), respectively (total 136 out of 152 [89.5%]). No significant increase in early or long-term adverse events was associated with retrograde popliteal access. Conclusions: Whenever standard access sites do not enable successful recanalization of SFA occlusions, retrograde popliteal access can be safely and effectively envisioned as bail-out strategy. © 2012 Wiley Periodicals, Inc.