This study evaluated the usefulness of the Human Activity Profile (HAP) in people with knee osteoarthritis (OA). People with OA (N = 226) completed the HAP and a battery of pain and physical function measures. Healthy elderly controls (N = 33) also completed the HAP, and 20 OA participants underwent repeat testing 2 to 7 days later. Test-retest reliability was excellent (intraclass correlation coefficients 0.96 and 0.95). The HAP was sensitive enough to detect differences in physical activity between people with (N = 33) and without OA (N = 33) (p < 0.01). When OA individuals were classified as impaired, moderately active, or active based on HAP score, differences in pain and physical function were detected (p < 0.05). Correlations between HAP and commonly used pain and physical function measures were weak to moderate (r = 0.18-0.63, all p < 0.01), indicating that the HAP measures additional information not gained by other assessment tools. The HAP is a reliable measure, and it is sensitive enough to discriminate between people with and without knee OA, and within an OA cohort. The HAP appears to have greater applicability in osteoarthritic women than men.