Osteochondral lesions of the talus (OLTs) may progress to ankle arthritis needing ankle arthroplasty or arthrodesis. We report five cases of OLTs treated along the principles developed for chondrogenesis of the knee joint with autologous peripheral blood stem cells (PBSCs), resulting in repair and regeneration of the bone and cartilage components. Improvement in Ankle Osteoarthritis Scale (AOS) scores with minimum two years follow-up showed statistical significance (p < 0.05).