BACKGROUND:Progression of tibiofemoral (TF) and patellofemoral (PF) osteoarthritis (OA) and changes in knee function more than 15 years after anterior cruciate ligament reconstruction (ACLR) are not well understood. PURPOSE:To examine the progression of knee OA and changes in symptoms and function in isolated and combined injuries from 15 to 20 years after ACLR. STUDY DESIGN:Cohort study; Level of evidence, 2. METHODS:A total of 210 subjects with ACLR were prospectively followed. At the 15- and 20-year follow-ups, radiographs were obtained and classified by the Kellgren and Lawrence (K-L) grading system. Symptoms and function were evaluated with the Knee injury and Osteoarthritis Outcome Score (KOOS) as well as isokinetic quadriceps and hamstring muscle strength tests. RESULTS:There were 168 subjects (80%) who returned for the 20-year follow-up, with a mean (±SD) age of 45 ± 9 years, mean body mass index of 27 ± 4, and median Tegner activity level of 4 (range, 0-9). The prevalence of radiographic TF and PF OA at the 20-year follow-up was 42% and 21%, respectively. Patients with ACL injuries and other combined injuries had significantly higher prevalence of radiographic TF OA compared with those who had isolated ACL injury (P < .0001). There was a 13% increase in radiographic TF OA (P = .001) and an 8% increase in PF OA (P = .015) from the 15- to the 20-year follow-up. A significant deterioration in knee symptoms and function was observed on the KOOS subscales (P ≤ .01), with the exception of quality of life (P = .14), as well as a decrease in quadriceps muscle strength and hamstring muscle strength (P < .0001). CONCLUSION:The prevalence of radiographic TF and PF OA was 42% and 21%, respectively. A significantly higher prevalence of TF OA was found for subjects with combined injuries compared with those who had isolated ACL injury. The majority of the subjects were stable radiographically over the 5 years between follow-ups. A statistically significant deterioration in symptoms and function was noted, but the mean changes were of questionable clinical importance.