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While depression after stroke is common and stroke prevalence globally increases in working age populations, the role of return-to-work (RTW) in the pathogenesis of post-stroke depression (PSD) remains unclear. This study examined if RTW is linked to PSD within the first year after ischemic stroke,  independently  from established risk factors. Stroke survivors ( n  = 176) in their working age (&lt;65 years) recruited from two rehabilitation clinics were assessed for established risk factors: pre-stroke depression, activities of daily living, stroke severity, cognitive impairment, and social support. RTW and depressive symptoms (Geriatric Depression Scale: GDS-15) were assessed six- and twelve-months post-stroke. Multivariate regression analyses were used to assess the cross-sectional and longitudinal relationship between RTW and GDS-15, while controlling for established PSD risk factors. Successful RTW was independently associated with lower GDS-15 at both measurement occasions ( p  &lt; .05), next to the absence of pre-stroke depression and higher social support. Stroke severity predicted GDS-15 at twelve months. The predictive value of six-months RTW for  subsequent  depressive symptoms  beyond  the influence of established risk factors was  ß  = −1.73 ( p  = .09). RTW was independently associated with PSD in young stroke survivors within the first-year post-stroke, and exerted a (marginally significant) effect on subsequent depression. Our study highlights the relevance of RTW for young stroke survivors’ PSD,  beyond  the influence of established risk factors. Further assessments examining to what extent fostering RTW contributes to mental well-being after stroke might be promising for PSD prevention, next to evident beneficial economic effects.

Return to work and depressive symptoms in young stroke survivors after six and twelve months: cross-sectional and longitudinal analyses