Background: To evaluate the clinical outcomes and second-look arthroscopic findings after intra-articular adipose-derived regenerative cell (ADRC) injection as treatment for knee osteoarthritis (OA). Methods: ADRCs were administered to 11 patients (19 knees; mean age, 61.7 years) with knee OA. Subcutaneous adipose tissue was harvested by liposuction from both thighs, and arthroscopic lavage was performed, followed by ADRC injection (mean dose, 1.40 × 10 7 cells) into the synovial fluid. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Lysholm score, and visual analog scale score. Arthroscopic examinations were performed to assess the International Cartilage Repair Society cartilage injury grade preoperatively and overall repair postoperatively. Noninvasive assessments were performed at baseline and at 1-, 3-, and 6-month follow-ups; arthroscopic assessments were performed at baseline and at 6 months. Results: All outcome measures significantly improved after treatment. This improvement was evident 1 month after treatment and was sustained until the 6-month follow-up. Data from second-look arthroscopy showed better repair in low-grade cartilage lesions than in lesions with a greater degree of damage. No patients demonstrated worsening of Kellgren-Lawrence grade, and none underwent total knee arthroplasty during this period. Conclusions Clinical outcomes were improved in patients with knee OA after ADRC administration. Cartilage regeneration was more effective in smaller damaged lesions than in bigger lesions.