We conducted a systematic review to evaluate the associations of knee alignment or trochlear morphology (measured on imaging) with presence, severity, onset, and/or progression of patellofemoral osteoarthritis (PFOA).We prospectively registered our protocol with PROSPERO (International prospective register of systematic reviews) and followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to report this review. We searched 10 electronic databases, screened citing articles, and reviewed reference lists. We extracted data and evaluated methodologic quality. Due to study design heterogeneity, we used a best-evidence synthesis to summarize the evidence.We included 16 publications (2,892 participants, 66% women) after removing 4 papers that did not meet our threshold for methodologic quality. There were 11 cross-sectional and 5 longitudinal papers. The target population was knee OA in 11 studies, PFOA in 2 studies, and other knee conditions in 3 studies. Alignment or morphology was measured using radiographs in 8 studies, magnetic resonance imaging in 7 studies, and computed tomography in 2 papers. Limitations include substantial heterogeneity in samples and methods, short followup times in longitudinal studies, and a small number of studies that specifically recruited participants with PFOA.There is strong evidence that PFOA is associated with both trochlear morphology and frontal plane knee alignment, while evidence is limited but consistent in the sagittal and axial planes. These findings suggest that alignment should be evaluated clinically in individuals with PFOA. Clinical interventions targeting knee alignment warrant further investigation.