Objective. To identify factors related to single-leg standing balance in individuals with medial compartment knee osteoarthritis (OA). Methods. This cross-sectional study assessed clinical, demographic, and biomechanical measures in 57 individuals and their relationships with single-leg standing balance. Differences in age, mass, symptoms, knee pain, radiographic severity, lower extremity alignment, and hip and knee extension as well as hip abduction torques were compared between those who could and could not perform 3 trials of single-leg standing balance. Multiple regression was used to identify predictors of center of pressure (COP) path length in those who could complete the task. Results. Thirty-four individuals (60%) successfully completed all 3 single-leg standing balance trials and were significantly younger (P ؍ 0.003) than those who could not. No other variable was significantly different between the groups. Disease severity, number of painful knees, lower extremity alignment, pain intensity, and quadriceps torque were all significant predictors of COP path length. Specifically, better single-leg standing balance (smaller COP path length) was related to more severe radiographic changes and stronger quadriceps, those with bilateral symptoms, and to less varus malalignment and knee pain. Conclusion. Single-leg standing balance in those with medial knee OA is related to the modifiable factors lower extremity alignment, knee pain, and quadriceps strength. Given the reduced balancing ability in this patient population, interventions targeting these factors are necessary.