A few case-control studies of multiple system atrophy (MSA) have been reported in Western populations. In this study, we included various epidemiological factors to evaluate whether the risk factors for MSA differed in Korean and Western populations. A total of 100 consecutive MSA patients and 104 controls at two referral hospitals participated. Information was obtained through face-to-face interviews using a structured questionnaire: history of living area, occupational history, food habits, alcohol and tobacco consumption, and use of drugs. Odds ratios and 95% confident intervals (OR [95% CI]) were computed using logistic regression. The multivariate logistic regression analysis revealed that use of antihypertensive medication (OR = 0.30 [0.12-0.78]) and vitamins (OR = 0.30 [0.14-0.64]) and consumption of meat and poultry (OR = 0.27 [0.13-0.56]) were associated with decreasing risk for MSA, whereas use of herbal medications (OR = 3.17 [1.28-7.84]) was associated with increasing risk for MSA. In univariate analysis adjusted for age, sex, education level, and recruitment center, use of aspirin (OR = 0.21 [0.07-0.61]) and coffee consumption (OR = 0.44 [0.23-0.84]) were significantly less frequent in MSA patients than in controls, whereas heavy smoking (≥40 pack-years) was significantly more prevalent in MSA patients than in controls (OR = 3.44 [1.05-11.23]). There was no difference in living area, participation in farming, or exposure to agrichemicals and solvents between groups. This study showed that MSA in Korea is characterized by risk factors that are both similar to and different from those affecting Western populations and that herbal medicines constitute a new MSA risk factor for the Korean population.