This pilot study examined the long-term structural changes in the osteochondral unit of 20 patients with knee osteoarthritis (KOA) who underwent high tibial osteotomy (HTO) and received post-treatment with either platelet-rich plasma (PRP) or stromal vascular fraction (SVF). Ten patients were injected with autologous PRP (PRP subgroup), while another ten patients received autologous SVF (SVF subgroup) six weeks after surgery and were monitored for 18 months. Histological samples of bone and cartilage (2 mm in diameter and 2 cm long) were taken from tibial and femoral sites during surgery and 18-month post-HTO, and morphometric analyses were conducted using Mega-Morf12 software. Both post-treatment resulted in an increase in articular cartilage height at both sites (p < 0.001 in the tibia and femur), indicating positive outcomes. Significant improvements in subchondral and trabecular bone architecture were also observed, with SVF injection showing higher reparative capacity in terms of bone volume (p < 0.001 for the tibia and p = 0.004 for the femur), subchondral bone height (p < 0.001 for the tibia and p = 0.014 for the femur), trabecular bone volume (p < 0.001 for the femur), and intertrabecular space (p = 0.009 for the tibia and p = 0.007 for the femur). This pilot study, for the first time, demonstrates that HTO surgery combined with PRP and SVF post-treatments can lead to significant enhancements in knee articular cartilage and bone architecture in KOA patients, with SVF showing higher regenerative potential. These findings may contribute to improving treatment strategies for better clinical outcomes in HTO therapy for patients with KOA.