In our previous cross-sectional study, we found that restless legs syndrome (RLS) was associated with erectile dysfunction (ED). Thus, we conducted a prospective study to examine whether RLS was associated with a higher risk of developing ED based on 6 years of follow-up among 10,394 men (mean age = 63.4 years) in the Health Professionals Follow-up Study. RLS was assessed in 2002 using a set of standardized questions recommended by the International RLS Study Group. Erectile function was assessed by means of questionnaires in 2000, 2004, and 2008. We identified 1,633 incident ED cases. Men with RLS were more likely to develop ED (relative risk = 1.38, 95% confidence interval: 1.14, 1.68; P = 0.001) than were those without the syndrome, after adjustment for potential confounders, such as age, body mass index, smoking, physical activity, other sleep disorders, and snoring status. A higher frequency of RLS symptoms was also associated with an increased risk of ED (P(trend) = 0.001). In conclusion, men with RLS had a higher risk of ED, and the magnitude of the risk increased with a higher frequency of RLS symptoms. Combinations of other sleep disorders with RLS further increased the risk of ED.