Stroke is one of the most common diseases and has several potential consequences, such as psychological problems and pain. Return to work (RTW) after stroke in working-age individuals is incomplete. The present study aimed to investigate differences in self-perceived general health, pain, and depression between 1 and 5 years post-stroke related to RTW status. The study was nationwide, registry-based and the study population (n = 398) consisted of working-age people who had a stroke in 2011 and participated in 1-year and 5-year follow-up questionnaire surveys. Shift analyses with the Wilcoxon signed rank test and logistic regression were used. RTW within the first year post-stroke was associated with better self-perceived general health, less pain, and less depression both at 1 and 5 years post-stroke, compared with the no-RTW group. However, the RTW group had significant deterioration in general health and pain between 1 and 5 years, while the no-RTW group had no significant change. RTW was a significant predictor of lower odds of improvement in general health and pain between 1 and 5 years. This emphasizes the need for continued follow-up and support to ensure a balance between work and health for RTW individuals after stroke.