Mesenchymal stem cells from several sources (bone marrow, synovial tissue, cord blood, and adipose tissue) can differentiate into variable parts (bones, cartilage, muscle, and adipose tissue), representing a promising new therapy in regenerative medicine. In animal models, mesenchymal stem cells have been used successfully to regenerate cartilage and bones. However, there have been no follow-up studies on humans treated with adipose-tissue-derived stem cells (ADSCs) for the chondromalacia patellae. To obtain ADSCs, lipoaspirates were obtained from lower abdominal subcutaneous adipose tissue. The stromal vascular fraction was separated from the lipoaspirates by centrifugation after treatment with collagenase. The stem-cell-containing stromal vascular fraction was mixed with calcium chloride-activated platelet rich plasma and hyaluronic acid, and this ADSCs mixture was then injected under ultrasonic guidance into the retro-patellar joints of all three patients. Patients were subjected to pre- and post-treatment magnetic resonance imaging (MRI) scans. Pre- and post-treatment subjective pain scores and physical therapy assessments measured clinical changes. One month after the injection of autologous ADSCs, each patient's pain improved 50-70%. Three months after the treatment, the patients' pain improved 80-90%. The pain improvement persisted over 1 year, confirmed by telephone follow ups. Also, all three patients did not report any serious side effects. The repeated magnetic resonance imaging scans at three months showed improvement of the damaged tissues (softened cartilages) on the patellae-femoral joints. In patients with chondromalacia patellae who have continuous anterior knee pain, percutaneous injection of autologous ADSCs may play an important role in the restoration of the damaged tissues (softened cartilages). Thus, ADSCs treatment presents a glimpse of a new promising, effective, safe, and non-surgical method of treatment for chondromalacia patellae.