Background: Focal cartilage lesions in the patellofemoral (PF) joint are common. Several studies correlated PF risk factors with PF instability, anterior knee pain, and PF arthritis; however, there is a lack of evidence correlating those factors to PF focal cartilage lesions. Purpose: To evaluate the influence of the anatomic PF risk factors in patients with isolated focal PF cartilage lesions. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients with isolated PF focal cartilage lesions were included in the cartilage lesion group, and patients with other pathologies and normal PF cartilage were included in the control group. Multiple PF risk factors were accessed on magnetic resonance imaging scans: patellar morphology (patellar width, patellar thickness, and patellar angle), trochlear morphology (trochlear sulcus angle, lateral condyle index, and trochlear sulcus depth), patellar height (Insall-Salvati ratio and Caton-Deschamps index), axial patellar positioning (patellar tilt, angle of Fulkerson), and quadriceps vector (tibial tuberosity–trochlear groove distance). Results: A total of 135 patients were included in the cartilage lesion group and 100 in the control group. As compared with the control group, the cartilage lesion group had a higher sulcus angle (P = .0007), lower trochlear sulcus depth (P < .0001), lower angle of Fulkerson (P < .0001), lower patellar width (P = .0003), and higher Insall-Salvati ratio (P < .0001). From the patients in the cartilage lesion group, 36% had trochlear dysplasia; 27.6%, patella alta; and 24.7%, abnormal patellar tilt. These parameters were more frequent in the cartilage lesion group (P < .0001). Trochlear lesions were more frequent in men, presented at an older age, and had fewer associated anatomic risk factors. Patellar lesions, conversely, were more frequent in women, presented at younger age, and were more closely associated with anatomic risk factors. Conclusion: PF anatomic abnormalities are significantly more common in patients with full-thickness PF cartilage lesions. Trochlear dysplasia, patella alta, and excessive lateral patellar tilt are the most common correlated factors, especially in patellar lesions.