Osteoarthritis of the knee is seen more frequently in females than males. However, few studies have examined the interplay of gender, gait mechanics, pain, and disability in persons with osteoarthritis. This study examines the influence of anthropometrics, radiographic disease severity, pain, and disability on gender differences in gait mechanics in patients with knee osteoarthritis. Gait mechanics for 26 men and 30 women were collected using 3-D kinematics and kinetics. Women had a significantly lower knee adduction moment than men and a significantly higher stride frequency. Within female subjects, variations in gait mechanics were primarily explained by weight, BMI, pain, and disability. In males, variations in gait mechanics were primarily explained by age and disability.