The use of synthetic oxytocin (OT) to induce and/or augment labor and delivery is on the rise. Maternal exposure to OT during birth may have adverse effects on the infant's development, including increased risk for autism. Yet, studies that test this biologically plausible association and whether it is modified by sex are limited and show inconsistent findings. To this end, we conducted an epidemiological analysis, including all singleton live births in Denmark between 2000 and 2009 (N = 557,040), with a follow-up through 2012. A total of 2110 children in this cohort were subsequently diagnosed with autistic disorder according to the ICD-10-DCR. Augmentation of labor with OT was modestly associated with an increased risk for autism in males (HR 1.13; 95% CI, 1.00–1.26; P = 0.04), but not in females (0.99; 0.77–1.27; P = 0.95). Among males exposed to OT augmentation, 560 were subsequently diagnosed with autistic disorder, and among those not exposed, 1177 met criteria for autism (incidence rate 103.2 and 81.4 per 100,000 person-years, respectively). Our findings suggest a modest association between OT-augmented labor and risk for autism in males. However, given the known benefits of using synthetic OT during labor and delivery caution is warranted when interpreting the findings. Future studies should also investigate dose-dependent effect of OT on infant's development.