OBJECTIVE: To estimate the direct and indirect osteoarthritis (OA)-attributable costs and predictors of costs of knee and hip OA in Spain. METHODS: This study included consecutive patients age > or = 50 years with symptomatic and radiologic knee and/or hip OA who were seen at primary care centers in all provinces of Spain. Information on demographics, health status (Short Form 12 Health Survey), comorbidities (Charlson Index), clinical (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) and radiologic OA severity (Kellgren/Lawrence [K/L] scale), data related to OA health resources utilization (medical and nonmedical), and subjects' and caregivers' expenses and time lost in the previous 6 months were collected in 2 separate, structured, and detailed interviews. Costs in euros were assigned using market prices and official sources if available, and were annualized (to 2007). The predictors of costs were assessed in multivariate regression models. Costs were log-transformed before being modeled. RESULTS: A total of 1,071 subjects were analyzed (74% women, mean +/- SD age 71 +/- 9 years). Average total annual costs were euro1,502 per patient. Direct costs accounted for 86% of the total cost. We estimated a national cost of euro4,738 million, representing 0.5% of the gross national product. Higher total costs were associated with comorbidity (Charlson Index odds ratio [OR] 1.27, 95% confidence interval [95% CI] 1.03-1.58), poorer health status (P < 0.050), worse WOMAC scores (OR 1.05, 95% CI 1.03-1.08), and grade 4 K/L scores (OR 1.76, 95% CI 1.15-2.69). CONCLUSION: The economic burden of knee and hip OA is substantial. Costs increased with comorbidity, poorer health status, and clinical and radiologic OA severity.