Background. In line with patient-centered health care, it is necessary to understand patients’ perceptions of health. How stroke survivors perceive their health at different time points after stroke and which factors are associated with these feelings provide important information about relevant rehabilitation targets. Objective. This study aimed to identify the independent factors of health-related quality of life (HRQoL) from a biopsychosocial perspective using the methods of multivariate regression at 3 different time points poststroke. Methods. Included in the study were 99 patients from stroke units with diagnosed first-ever stroke. At admission and at 6 weeks, 3 months, and 1 year poststroke, HRQoL was assessed using the EuroQoL-5D Visual Analogue Scale (EQ-5D VAS). Consequences in Body Functions and Activities and Participation, and Environmental Factors were documented using 155 categories of the International Classification of Functioning, Disability and Health (ICF) Core Set for Stroke. Results. For a period of 1 year, problems with recreation and leisure, personality functions, energy and drive functions, and gait pattern functions were repeatedly associated with worse HRQoL. Whereas Body Functions and Activities and Participation explained more than three-fourths of the variances of HRQoL at 6 weeks and 3 months (R ² = 0.80-0.93), the variation at 1 year was best explained by either Body Functions or Environmental Factors (R ² = 0.51). Conclusions. The results indicate the importance of Body Functions and Activities and Participation (mainly personality functions and recreation and leisure) on HRQoL within 3 months poststroke, but increased impact of Environmental Factors on HRQoL at 1 year.