OBJECTIVES: The goal of this study was to analyze changes in disease-specific HRQoL over time. METHODS: The Stroke Impact Scale (SIS) was administered to 33 first-time stroke survivors discharged home from the hospital at baseline, 3, 6, 9 and 12 months as part of a larger NIH-funded study. The SIS was administered to this same cohort again at a sixth time point. The average time since initial stroke to the sixth time point ranged from 1.6 to 4.04 years, with an average of 2.67 years. RESULTS: Of the 33 patients, 78.8% were male, 67% had mild stroke, 24% had moderate stroke, and 9% had severe stroke. The average age was 68 years (range, 53 to 87 years). A linear mixed model for repeated measures showed statistically significant changes over time for all subcomponents of the SIS: physical, emotion, memory and social participation component scores increased significantly (p<0.001), while communication scores decreased significantly over the same time period (p=0.02). However, statistically significant decreases in scores were seen between 12 month SIS scores and the additional sixth time point score for social participation (p=0.03), memory (p=0.02), and communication (p=0.3). A significant increase for this same time period was demonstrated for emotion (p=<0.001). CONCLUSION: Increases in physical, emotion, memory and social participation component scores demonstrated a significant improvement over an initial 12 month period. However, significant decreases in social participation, memory and communication were seen for the time period between the 12 month score and scores at least one and a half to four years later. These results suggest that while there may be significant physical and cognitive improvements during the first year post stroke, individuals were experiencing difficulties with social reintegration, communication and memory at later time points. Results from this preliminary study demonstrate the need for continued, longitudinal research on HRQoL in long-term stroke survivors.