STUDY DESIGN: Controlled laboratory study, cross-sectional data. OBJECTIVES: To investigate isometric knee flexion and extension strength, failure of voluntary muscle activation, and antagonist cocontraction of subjects with knee osteoarthritis (OA) compared with age-matched asymptomatic control subjects. BACKGROUND: Quadriceps weakness is a common impairment in individuals with knee OA. Disuse atrophy, failure of voluntary muscle activation, and antagonist muscle cocontraction are thought to be possible mechanisms underlying this weakness; but antagonist cocontraction has not been examined during testing requiring maximum voluntary isometric contraction. METHODS: Fifty-four subjects with knee OA (mean ± SD age, 65.6 ± 7.6 years) and 27 similarly aged control subjects (age, 64.2 ± 5.1 years) were recruited for this study. Isometric knee flexion and extension strength were measured, and electromyographic data were recorded, from 7 muscles crossing the knee and used to calculate cocontraction ratios during maximal effort knee flexion and extension trials. The burst superimposition technique was used to measure failure of voluntary activation. RESULTS: Knee extension strength of subjects with knee OA (mean ± SD, 115.9 ± 6.7 Nm) was significantly lower than for those in the control group (152.3 ± 9.6 Nm). No significant between-group difference was found for failure of voluntary muscle activation, or the cocontraction ratios during maximum effort knee flexion or extension. CONCLUSION: These results demonstrate that the reduction in isometric extension strength, measured with a 90° knee flexion angle, in subjects with knee OA is not associated with increased antagonist cocontraction.