OBJECTIVE: To analyze the clinical outcomes, knee function, and activity level of patients after treatment of full-thickness cartilage defects involving the patellofemoral compartment of the knee with cryopreserved osteochondral allograft. DESIGN: Nineteen patients with cartilage defects involving the patellofemoral compartment were treated. The average age was 31 years (range 15-45 years), including 12 females and 7 males. Patients were prospectively followed using validated clinical outcome measures including Veterans RAND 12-item Health Survey (VR-12), International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Tegner activity scale. Graft incorporation was evaluated by magnetic resonance imaging (MRI) or second-look arthroscopy. RESULTS: The cartilage defects included the patella (n = 16) and the femoral trochlea (n = 3). Mean VR-12 scores increased from 31.6 to 46.3 (P < 0.01), mean IKDC increased from 40.0 to 69.7 (P < 0.01), mean KOOS increased from 53.9 to 80.2 (P < 0.01), and mean Tegner scores increased from 3.0 to 4.9 (P < 0.01), at average follow-up of 41.9 months (range 24-62 months). Of the 3 patients who underwent second-look arthroscopy, all demonstrated a well-incorporated graft. Mean MOCART score for the 6 patients with follow-up MRI was 62.5 (range 25-85). The reoperation rate was 21.1% and 2 patients (12.5%) experienced progressive patellofemoral osteoarthritis requiring conversion to patellofemoral arthroplasty. CONCLUSION: Patients with unipolar cartilage defects involving the patellofemoral compartment of the knee can have positive outcomes at minimum 2-year follow-up after surgical treatment with a cryopreserved osteochondral allograft when concomitant pathology is also addressed, but the reoperation rate is high and bipolar cartilage lesions may increase the failure rate.