Purpose: To assess the associations of meniscal tears, knee malalignment, cartilage damage, knee effusion, and body mass index with meniscal extrusion. Materials and Methods: The Multicenter Osteoarthritis study is an observational study of individuals who have or are at risk for knee osteoarthritis (OA). The HIPAA-compliant protocol was approved by the institutional review boards of all participating centers, and written informed consent was obtained from all patients. All subjects with available baseline knee radiographs and magnetic resonance (MR) images were included. MR imaging assessment of meniscal morphologic characteristics, meniscal position, and cartilage morphologic characteristics with use of the Whole-Organ Magnetic Resonance Imaging Score system was performed by two musculoskeletal radiologists. Cross-sectional associations of severity of meniscal tears, knee malalignment, tibiofemoral cartilage damage, knee effusion, and body mass index with meniscal extrusion were assessed by using logistic regression, with multiadjustments when testing each predictor. Results: A total of 1527 subjects (2131 knees; 2116 medial and 2106 lateral menisci) were included. Medially, meniscal tears, varus malalignment, and cartilage damage were associated with meniscal extrusion, with odds ratios (ORs) of 6.3 (95% confidence interval [CI]: 5.0, 8.0), 1.3 (95% CI: 1.1, 1.7), and 1.8 (95% CI: 1.4, 2.2), respectively. Laterally, meniscal tears, valgus malalignment, and cartilage damage were associated with meniscal extrusion, with ORs of 10.3 (95% CI: 7.1, 14.9), 2.2 (95% CI: 1.5, 3.2), and 2.0 (95% CI: 1.3, 2.9), respectively. Conclusion: Meniscal tears are not the only factors associated with meniscal extrusion; other factors include knee malalignment and cartilage damage. Meniscal extrusion is probably an effect of the complex interactions among joint tissues and mechanical stresses involved in the OA process. © RSNA, 2012.