OBJECTIVE: Based on converging observations in animal, clinical and ecological studies, we hypothesised a possible impact of ritual circumcision on the subsequent risk of autism spectrum disorder (ASD) in young boys. DESIGN: National, register-based cohort study. SETTING: Denmark. PARTICIPANTS: A total of 342,877 boys born between 1994 and 2003 and followed in the age span 0-9 years between 1994 and 2013. MAIN OUTCOME MEASURES: Information about cohort members' ritual circumcisions, confounders and ASD outcomes, as well as two supplementary outcomes, hyperkinetic disorder and asthma, was obtained from national registers. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status were obtained using Cox proportional hazards regression analyses. RESULTS: With a total of 4986 ASD cases, our study showed that regardless of cultural background circumcised boys were more likely than intact boys to develop ASD before age 10 years (HR = 1.46; 95% CI: 1.11-1.93). Risk was particularly high for infantile autism before age five years (HR = 2.06; 95% CI: 1.36-3.13). Circumcised boys in non-Muslim families were also more likely to develop hyperkinetic disorder (HR = 1.81; 95% CI: 1.11-2.96). Associations with asthma were consistently inconspicuous (HR = 0.96; 95% CI: 0.84-1.10). CONCLUSIONS: We confirmed our hypothesis that boys who undergo ritual circumcision may run a greater risk of developing ASD. This finding, and the unexpected observation of an increased risk of hyperactivity disorder among circumcised boys in non-Muslim families, need attention, particularly because data limitations most likely rendered our HR estimates conservative. Considering the widespread practice of non-therapeutic circumcision in infancy and childhood around the world, confirmatory studies should be given priority.