UNLABELLED: The aim of the current study was to estimate the prevalence and time trend of invalidating musculoskeletal pain in the Spanish population and its association with socio-demographic factors, lifestyle habits, self-reported health status, and comorbidity with other diseases analyzing data from 1993-2006 Spanish National Health Surveys (SNHS). We analyzed individualized data taken from the SNHS conducted in 1993 (n = 20,707), 2001 (n = 21,058), 2003 (n = 21,650) and 2006 (n = 29,478). Invalidating musculoskeletal pain was defined as pain suffered from the preceding 2 weeks that decreased main working activity or free-time activity by at least half a day. We analyzed socio-demographic characteristics, self-perceived health status, lifestyle habits, and comorbid conditions using multivariate logistic regression models. Overall, the prevalence of invalidating musculoskeletal pain in Spanish adults was 6.1% (95% CI, 5.7-6.4) in 1993, 7.3% (95% CI, 6.9-7.7) in 2001, 5.5% (95% CI, 5.1-5.9) in 2003 and 6.4% (95% CI 6-6.8) in 2006. The prevalence of invalidating musculoskeletal pain among women was almost twice that of men in every year (P < .05). The multivariate analysis showed that occupational status (unemployed), sleep <8 hours/day and having any accident in the preceding year were significantly associated in both gender with a higher likelihood of suffering from invalidating musculoskeletal pain among Spanish adults. Within men, other predictors of invalidating musculoskeletal pain were to be married and lower educational level, whereas in women were age of 45-64 years old (OR 1.89, 95% CI 1.32-2.7), obesity (OR 1.23, 95% CI 1.06-1.42), a sedentary lifestyle (OR 1.23, 95% CI 1.06-1.42), and presence of comorbid chronic diseases (OR 1.32, 95% CI 1.14-1.53). Further, worse self-reported health status was also related to a greater prevalence of invalidating musculoskeletal pain (OR 6.88, 95% 5.62-8.40 men, OR 7.24, 95% 6.11-8.57 women). Finally, we found that the prevalence of invalidating musculoskeletal pain increased from 1993 to 2001 for both men (OR 1.31, 95% 1.08-1.58) and women (OR 1.19, 95% 1.03-1.39) with no significant increase from the remaining surveys. Our results suggest that invalidating musculoskeletal pain deserves an increased awareness among health professionals. More educational programs which address postural hygiene, physical exercise, and how to prevent obesity and sedentary lifestyle habits should be provided by Public Health Services. PERSPECTIVE: This population-based study indicates that invalidating musculoskeletal pain that reduces main working activity is a public health problem in Spain. The prevalence of invalidating musculoskeletal pain was higher in women than in men and associated to lower income, poor sleeping, worse self-reported health status, and other comorbid conditions. Further, the prevalence of invalidating musculoskeletal pain increased from 1993 to 2001, but remained stable from the last years (2001 to 2006).