BACKGROUND AND PURPOSE: Little information is available about change in health-related quality of life (HRQoL) during the first few months following acute stroke, and whether baseline variables can predict who will have the largest improvement in HRQoL. This study assessed the change in HRQoL from 1 to 6 months following acute stroke and the determinants of these changes. METHODS: Patients >60 years of age, who had experienced an acute stroke and were admitted to hospital within 24 h of onset, were followed longitudinally. HRQoL was assessed with the Short Form 36 (SF-36) health status questionnaire. RESULTS: Of 550 eligible stroke patients, 315 fulfilled the inclusion criteria and were alive after 30 days. At 1 month, 179 patients responded to the questionnaire, of whom also 140 responded at 6 months following acute stroke. From 1 to 6 months following stroke, all dimensions of the SF-36 improved. The magnitude of change was largest on the role-physical and role-emotional scales and lowest on the bodily pain and mental health scales. Higher physical component summary (PCS) score at 1 month was associated with lower odds of being above the 75th percentile of change in PCS score between the assessments, and higher baseline mental component summary (MCS) score was associated with lower odds of being above the 75th percentile of change in MCS. Treatment in a stroke unit was associated with an increase in the MCS score and higher neurological score with an increase in PCS score of the SF-36. CONCLUSION: This prospective study showed a considerable improvement in HRQoL from 1 to 6 months after stroke; however, no baseline variables except baseline scores were associated with changes in HRQoL during the 5-month period.