Recent data showed that soccer players in Italy had an unusually high risk of amyotrophic lateral sclerosis (ALS) and that repeated head trauma might have contributed to this increase. The authors examined whether head injury was related to ALS risk in a case-control study of 109 New England ALS cases diagnosed in 1993-1996 and 255 matched controls. They also conducted a meta-analysis of the published literature. Overall, ever having experienced a head injury was nonsignificantly associated with a higher ALS risk. When compared with persons without a head injury, a statistically significant ALS risk elevation was found for participants with more than one head injury (odds ratio (OR) = 3.1, 95 percent confidence interval (CI): 1.2, 8.1) and patients who had had a head injury during the past 10 years (OR = 3.2, 95 percent CI: 1.0, 10.2). For participants who had had multiple head injuries with the latest occurring in the past 10 years, risk was elevated more than 11-fold. The meta-analysis also indicated a moderately elevated risk of ALS among persons with previous head injuries (OR = 1.7, 95 percent CI: 1.3, 2.2). In this study population, physical injuries to other body parts, including the trunk, arms, or legs, were not related to ALS risk. These data support the notion that head injury may increase the risk of ALS.