Our objective was to examine whether severe head injury, subtypes of head injury, or repeated head injuries are associated with ALS risk based on the Swedish population and health registers. We conducted a case-control study, nested within a cohort of 5,764,522 individuals who were born in Sweden during 1901-1970 and followed between 1991 and 2007. The study included 4004 ALS patients identified from the Swedish Patient Register during follow-up and 20,020 randomly selected controls matched by gender and birth year. We evaluated hospitalization for severe head injury that was recorded in the inpatient register before ALS diagnosis. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results showed that there was an association of ALS risk with severe head injury ≤ 1 year before diagnosis (OR: 3.9, 95% CI 2.6-6.1). No association was observed for severe head injury > 3 years before ALS diagnosis, nor was ALS associated with subtypes of head injury or repeated injuries occurring > 3 years before diagnosis. In conclusion, our findings from the Swedish registers provide no strong support for an etiological relationship between severe head injury in adulthood and ALS risk.