OBJECTIVES: To describe the association between physical disability and early exit from work in patients with clinically confirmed knee osteoarthritis (OA). METHODS: We analyzed data from the population-based EpiReumaPt study (Sep2011-Dec2013). 10,661 inhabitants were surveyed to capture all cases of rheumatic diseases within a representative sample of the population. We analyzed all participants aged 50-64, near the official retirement age and all knee OA cases were clinically validated, according to the ACR classification criteria. Disability was measured according with the Health Assessment Questionnaire (HAQ) with score of 0-3, 0 meaning no loss of physical function and 3 full disability. The association of disability and early exit from work was tested using individual level logistic regression. RESULTS: The Portuguese population aged between 50 and 64 who were out of paid work (51.8%) had a knee OA prevalence of 18.6% (women: 26.0%; men: 11.5%) and worst average HAQ score compared with those employed (0.47 vs. 0.28, respectively. p=0.0002). knee OA patients with higher levels of disability, measured by HAQ (scores ≥ 2) are at the greatest risk of early exit from work (80.7% vs. 67.4% for all knee OA population and 51.2% for those with HAQ scores ≥ 2 but without knee OA). We estimated an almost linear relationship between levels of disability and the probability of early exit from work, with its y-intercept increasing with the presence of knee OA. This association was independent from other relevant factors, such as age, comorbidities, education and household income (OR: 1.50; CI: 1.04-2.16; p=0.03). CONCLUSIONS: We observed an overall significant association between physical disability and premature withdrawal from employment. In particular, knee OA patients with higher levels of disability were at the highest risk of leaving the labor market. Decision makers should prioritize investments in policies targeting patients with disabling OA.