Purpose To evaluate whether mediopatellar plica and knee morphometric measurements obtained from magnetic resonance imaging (MRI) studies are associated with isolated medial patellofemoral osteoarthritis in young adults. Methods MRI studies from 60 patients with isolated medial patellofemoral osteoarthritis and 90 control patients with normal knee MRI studies were reviewed. The presence of mediopatellar plica, the presence of edema in the superolateral aspect of Hoffa's fat pad and suprapatellar fat pad, quadriceps and patellar tendinosis, and axial and sagittal alignment of the patellar and trochlear morphology were assessed using MRI. The relationship between mediopatellar plica, alignment, or morphology and the presence of isolated medial patellofemoral osteoarthritis was evaluated using logistic regression. Results Superolateral Hoffa's fat pad edema (odds ratio [OR] = 3.4, P = .009) and decreased trochlear sulcal angle (OR = 0.95, P = .045) were associated with increased odds of isolated medial patellofemoral osteoarthritis. Decreased lateral patellar tilt (OR = 0.93, P = .087) and patellar tendinosis (OR = 4.13, P = .103) trended toward being associated with increased odds of isolated medial patellofemoral osteoarthritis but were not statistically significant. No significant association was seen between the presence of mediopatellar plica and medial patellofemoral osteoarthritis (OR = 0.95, P = .353). Conclusions Medial patellofemoral osteoarthritis is associated with trochlear morphology and patellar alignment but not with mediopatellar plica.