Objectives: The objectives of this study have been to: 1) describe and compare urban and rural injured worker populations in Alberta, Canada; 2) identify return-to-work outcomes in urban and rural populations; 3) examine the relationship between geographic location of residence and recovery from work-related musculoskeletal injury; and 4) investigate if this relationship is attenuated after controlling for other known risk factors. Material and Methods: This study was a secondary analysis utilizing data of a population of musculoskeletal injury claimants who underwent clinical/RTW (return to work) assessment between December 2009 and January 2011 collected by the Workers’ Compensation Board of Alberta. Descriptive statistics were computed for 32 variables and used for comparing urban and rural workers. The logistic regression analysis was performed to test the association between geographic location of residence and likelihood of return-to-work. Results: Data on 7843 claimants was included, 70.1% of them being urban and 29.9% – rural. Rural claimants tended to have spent less time in formal education, have a blue-collar job, have no modified work available, have a diagnosed comorbidity, and not been enrolled in a specialized rehabilitation program. They were 1.43 (1.12–1.84) times the odds more likely than urban claimants to be continuing to receive full disability benefits 90 days after their RTW assessment, and 1.68 (1.06–2.67) times the odds as likely to report a recurrence of receiving disability benefits. Conclusions: Rural residence was associated with prolonged work disability, even after controlling for age, job type, education level, health utilization and other potential confounders. Further research is required to explore why injured workers in rural settings experience prolonged reception of disability benefits and have greater rates of recurrence of receiving disability benefits. Int J Occup Med Environ Health 2017;30(5):715–729