Evaluating factors that reduce stroke survivors' (SS) health-related quality of life (HRQOL) is important for developing interventions to improve HRQOL after stroke. The influence of baseline caregiver and family characteristics (physical health, depressive symptoms, family communication) on five domains of SS HRQOL (physical function, memory/thinking, social activities, communication, and mood) was examined. Data were collected on 132 SS-caregiver dyads at baseline, 4 months, and 12 months. Baseline caregiver depressive symptoms predicted lower scores for SS physical function and communication at 4 months and social participation and mood at 12 months. Male caregiver gender was negatively associated with SS HRQOL (communication and mood) at 12 months. Early intervention targeting these family characteristics, especially caregiver depressive symptoms, may improve survivors' HRQOL. © 2009 Wiley Periodicals, Inc. Res Nurs Health.