Purpose: To examine the association between adherence to physical activity guidelines and health-related quality of life (HRQOL) among individuals with arthritis. Methods: A cross-sectional sample with 33,071 US adults, 45 years or older with physician-diagnosed arthritis was obtained from 2007 Behavioral Risk Factor Surveillance System survey. We conducted negative binomial regression analysis to examine HRQOL as a function of adherence to physical activity guidelines controlling for physicians' recommendations for physical activity, age, sex, race, education, marital status, employment, annual income, health insurance, personal physician, emotional support, body mass index, activity limitations, health status, and co-morbidities based on Behavioral Model of Health Services Utilization. Results: Descriptive statistics showed that 60% adults with arthritis did not adhere to physical activity guidelines, mean physically and mentally unhealthy days were 7.7 and 4.4 days, respectively. Results from negative binomial regression indicated that individuals who did not adhere to physical activity guidelines had 1.14 days more physically unhealthy days and 1.12 days more mentally unhealthy days than those who adhered controlling for covariates. Conclusions: Adherence to physical activity is important to improve HRQOL for individuals with arthritis. However, adherence is low among this population. Interventions are required to engage individuals with arthritis in physical activity. © Springer Science+Business Media B.V. 2011.