Objective To evaluate the safety and effectiveness of tibiopedal and distal femoral access for retrograde crossing of chronic total occlusion (CTO) in Rutherford stage III to VI peripheral arterial occlusive disease, and to determine factors that correlate with technical success. Material and methods One hundred seventy-one consecutive patients were included in this retrospective study. Rutherford stages were III, IV, and V/VI in 24%, 8%, and 67% of patients. Inclusion criteria were CTO at the superficial femoral (SFA), popliteal (PA), and/or below-the-knee (BTK) level, and a failed antegrade treatment followed by a distal retrograde approach. The numbers of occluded vascular levels (OVL), lesion length, degree of calcification, technical success rate, complications, and clinical outcome were noted. Results OVL were 1 in 72%, 2 in 20%, and 3 in 8% of patients. CTOs were longer than 20 cm in 45.6% of cases and showed severe calcifications in 50.3%. Target vessels for distal access were the distal SFA/PA in 17% and BTK in 83%. The overall technical success rate was 82%. Severe calcification decreased technical success (p = 0.01) despite lesion length and Rutherford stage. Clinical outcome improved in 123/152 patients with a significant increase of the median ABI (N = 158) from 0.53 (interquartile range 0.39 to 0.61) to 0.85 (0.59 to 1.03; p < 0.001). Complications were reported in 7.6% cases with 2.3% related to the distal vascular access. Conclusion The tibiopedal and distal femoral retrograde access presents a safe and effective treatment option of CTOs at the thigh and/ or BTK after a failed antegrade attempt improving clinical outcome. Technical success decreased with lesion's degree of calcification. Key Points • Safety and effectiveness of the tibiopedal and distal femoral access for retrograde crossing of chronic total occlusion. • Target lesion's degree of calcification decreases technical success. • Complications related to the distal vascular access were rare.