The retrograde puncture of a distal artery is considered a bailout procedure in case of anterograde approach failure for peripheral artery disease (PAD) treatment. A single primary retrograde access has been suggested as an efficient and safe option. As scant data are available, we present our results using this approach. Between August 2019 and October 2022, we performed this technique in selected patients with femoro-popliteal PAD. Chronic total occlusions (CTOs) were selected on the basis of the CTOP classification. An ultrasound-guided retrograde puncture of a tibial artery at the ankle level was performed, followed by the preferential use of 4F materials. Hemostasis of the puncture site was obtained using manual compression. Postoperative duplex scan examination systematically included an evaluation of the punctured artery. Demographics, intraoperative, and follow-up data were collected retrospectively. The results are expressed as means with standard deviations and numbers with percentages when appropriate. In total, 55 procedures were performed in 46 patients (9 bilateral). Of these, 57% (N=26) were considered at risk for femoral puncture (obesity, history of groin surgery, challenging crossover approach) and 54% (N=25) presented with critical limb-threatening ischemia (CLTI). The TASC-II femoro-popliteal classification was generally B (60%) and also C (33%) or D (7%). Mean lesion length was 105.6±49.4 mm and 65% were CTOs. Most patients were operated in an outpatient setting (N=25; 54%) under potentialized local anesthesia (N=41, 89%). The punctured site was the posterior tibial artery in 73% (N=40). The procedure time was 65.1±25.7 minutes, and the fluoroscopy time was 10.7±8.5 minutes. The technical success rate was 100%. There were no intraoperative complications. All patients could walk the same day. One CLTI patient presented an erysipelas related to the puncture in postoperative period. At 30 days, the primary patency of the treated and the punctured arteries were 98% and 100%, respectively. A single primary retrograde access can be used safely to treat femoro-popliteal PAD. It represents a valuable alternative to the femoral puncture and allows fast ambulation. Prospective and long-term studies on larger populations are necessary to confirm our results. CONCLUSIONS This study demonstrates that a single primary retrograde access can be used safely without damaging the punctured artery to treat femoro-popliteal lesions, especially in claudicant patients. Chronic total occlusions can be treated successfully using this technique. This approach represents a valuable alternative to the femoral puncture and allows fast ambulation without risk of major bleeding.