Low‐density lipoprotein cholesterol (LDL‐C) levels are suggested to be associated inversely with Parkinson's disease (PD). To test the hypothesis that LDL‐C levels may increase PD risk, we studied a prospective cohort of 3,233 men (Honolulu‐Asia Aging Study) for whom the LDL‐C from fasting lipid profiles was obtained during 1991 to 1993. The cohort was followed longitudinally until 2001 for incident Parkinson's cases. During follow‐up, 41 men developed PD (18.4/10,000 person‐years). Although the incidence of PD increased with decreasing LDL‐C in a dose‐dependent manner, the association was only significant for men aged 71 to 75 years. In the latter group, risk of PD declined from 38.5/10,000 person‐years in men with LDL‐C levels <80 mg/dl to less than 9/10,000 person‐years for concentrations that were ≥140 mg/dl. After adjustment for age, smoking, coffee intake, and other factors, the relative odds of PD for men at the 80th versus the 20th percentile of LDL‐C (135 vs. 85 mg/dl) was 0.4 (95% confidence interval: 0.2, 0.9). This prospective study supports the hypothesis that low LDL‐C is associated with an increased risk of PD. Although confirmation is required, the underlying mechanisms may be useful in understanding key aspects of PD. © 2008 Movement Disorder Society