The objective was to estimate the prevalence of chronic widespread pain (CWP) and compare the quality-of-life (QoL), cardiovascular risk factors, comorbidity, complexity, and health costs with the reference population. A multicenter case-control study was conducted at 3 primary care centers in Barcelona between January and December 2012: 3048 randomized patients were evaluated for CWP according to the American College of Rheumatology definition. Questionnaires on pain, QoL, disability, fatigue, anxiety, depression, and sleep quality were administered. Cardiovascular risk and the Charlson index were calculated. We compared the complexity of cases and controls using Clinical Risk Groups, severity and annual direct and indirect health care costs. CWP criteria were found in 168 patients (92.3% women, prevalence 5.51% 95% confidence interval: 4.75%-6.38%). Patients with CWP had worse QoL (34.2 vs 44.1, P < 0.001), and greater disability (1.04 vs 0.35; P < 0.001), anxiety (43.9% vs 13.3%; P < 0.001), depression (27% vs 5.8%; P < 0.001), sleep disturbances, obesity, sedentary lifestyle, high blood pressure, diabetes mellitus, and number of cardiovascular events (13.1% vs 4.8%; P = 0.028) and higher rates of complexity, severity, hospitalization, and mortality. Costs were 3751 per year in patients with CWP vs 1397 in controls (P < 0.001). In conclusion, the average patient with CWP has a worse QoL and a greater burden of mental health disorders and cardiovascular risk. The average annual cost associated with CWP is nearly 3 times higher than that of patients without CWP, controlling for other clinical factors. These findings have implications for disease management and budgetary considerations.