Background: Multiple studies have demonstrated that a number of demographic and pathoanatomic characteristics are associated with patellofemoral instability, recurrence of instability, and less satisfactory results following medial patellofemoral ligament reconstruction (MPFL-R). Despite the growing volume of research, the relationship of risk factors to patient-reported outcome after MPFL-R is unclear. Purpose: To determine if certain pathoanatomic and demographic factors predict disease-specific quality-of-life outcome after isolated MPFL-R for symptomatic patellofemoral instability. Study Design: Cohort study; Level of evidence, 3. Methods: The study analyzed 224 isolated MPFL-Rs. Demographic data were collected, including age at first dislocation, sex, and presence of bilateral instability. Pathoanatomic risk factors included the presence of high-grade trochlear dysplasia, tibial tubercle–trochlear groove (TT-TG) distance, patella alta ratio, Beighton score, and patellar tilt. Other factors included femoral tunnel position accuracy and WARPS/STAID score. Descriptive analyses were conducted, followed by calculation of individual Spearman rank correlation coefficients for the predictor variables versus the Banff Patellofemoral Instability Instrument (BPII) scores. A multivariable regression with stepwise selection was employed to establish the final model predicting BPII score, with all significant variables for alpha ≤ .05 included in the final model. Results: The cohort of 224 patients included 66 (29.5%) males and 158 (70.5%) females, with a mean age of 24.1 years and a mean body mass index of 23.9 kg/m2. The mean age of first patellar dislocation was 15.7 years, and 41.4% of patients had bilateral instability. Pathoanatomic variables within the cohort included the following: high-grade trochlear dysplasia = 41%; mean TT-TG = 14.6 mm, with 16.8% of patients demonstrating a TT-TG ≥18 mm; mean Caton-Deschamps ratio = 1.09, with 22% of patients demonstrating a ratio ≥1.2; and positive Beighton score = 37.5%. The mean BPII score at postoperative 2 years was 67.1 out of 100. A stepwise elimination in the regression model demonstrated no statistically significant 3- or 2-way relationships. Assessment of individual variables indicated that bilateral symptoms ( P = .004), higher age at first dislocation ( P = .024), and femoral tunnel position >10 mm from the Schöttle point ( P = .042) were statistically significant predictors of lower quality-of-life scores. The R2 value for the regression analysis model was 0.07. Conclusion: In this large cohort of patients undergoing isolated MPFL-R for symptomatic lateral patellofemoral instability, a multivariable forward stepwise regression demonstrated that bilateral symptoms, femoral tunnel position, and age at first dislocation were statistically significant predictors of lower postoperative BPII scores. No anatomic risk factors were predictive of quality-of-life outcome score 2 years after MPFL-R surgery. The R2 value indicated that there were many other important contributing factors affecting BPII outcome scores than those explored in this study.