Objectives: To determine the prevalence and incidence of upper extremity (UE) and low back musculoskeletal pain (LBP) in two lower and middle-income Spanish-speaking countries (i.e., Costa Rica and Nicaragua) and Spain, a high income economy, and examine if the differences between countries are explained by physical, organizational, psychosocial and/or individual factors. Methods: A secondary analysis of office worker data collected as part of the multinational CUPID study in Costa Rica, Nicaragua and Spain, between 2007 and 2011. A total of 1020 subjects participated at baseline (96.4% of those approached) and 90.2 % at follow-up. Six outcome measures were created for each anatomical region, three on baseline prevalence: (1) pain in last 12 months, (2) pain in past month, (3) disabling pain; and three on incidence at follow-up: (4) pain in past month, (5) disabling pain, (6) persistence of pain. After stepwise selection of covariables (i.e., sociodemographic and work-related characteristics, physical demands, health beliefs, somatizing tendency, and mental health), multivariate logistic regression was used to estimate the association between country and each of these outcomes. Results: Prevalence and disabling UE pain were approximately 2-fold higher in Costa Rica and Nicaragua than in Spain. Incidence of UE was also between 2 and 3-fold higher. Prevalence and disabling LBP were higher in Costa Rica and Nicaragua than in Spain and the incidence was mostly higher in Nicaragua, as compared to Spain. Conclusion: Musculoskeletal pain was common in all three countries, with higher prevalence and incidence in Costa Rica and Nicaragua. Contrary to previous studies, our study shows that developing (low and middle income) economies might have higher prevalence and, in some instances, incidence of UE/LB pain as compared to Western or high-income economies (Spain). Differences among the three countries were only partially explained by the risk factors analyzed, possibly due to unmeasured factors such as ergonomic conditions, personal activities (hobbies, sports, home responsibilities, etc.), previous work exposure (work history), and/or compensation and public benefits systems.