This study examines the impact of fatigue on patients with Multiple Sclerosis (MS) and compares it to a group of hypertensive patients. The Fatigue Impact Scale (FIS) was administered to 85 MS patients and 20 hypertensive patients, along with assessments of neurologic impairment, mental health, and general health status. MS patients reported significantly higher fatigue impact compared to hypertensive patients, with fatigue being either their worst (14%) or one of their worst (55%) symptoms. Disease classification and neurologic impairment had little impact on FIS scores in the MS sample. The FIS was a significant factor in predicting mental health and general health status in the MS sample. The study highlights that fatigue is a prevalent and severe problem in MS, affects mental and general health, and cannot be predicted by clinical measures of neurologic impairment.This study examines the impact of fatigue on patients with Multiple Sclerosis (MS) and compares it to a group of hypertensive patients. The Fatigue Impact Scale (FIS) was administered to 85 MS patients and 20 hypertensive patients, along with assessments of neurologic impairment, mental health, and general health status. MS patients reported significantly higher fatigue impact compared to hypertensive patients, with fatigue being either their worst (14%) or one of their worst (55%) symptoms. Disease classification and neurologic impairment had little impact on FIS scores in the MS sample. The FIS was a significant factor in predicting mental health and general health status in the MS sample. The study highlights that fatigue is a prevalent and severe problem in MS, affects mental and general health, and cannot be predicted by clinical measures of neurologic impairment.