["Autism Research, EarlyView. ", "\nABSTRACT\nWhile the immediate benefits of labor epidural analgesia (LEA) are well established, recent studies have raised concerns about possible associations with autism spectrum disorder (ASD). Therefore, we examined the association between LEA and ASD in offspring. We analyzed data from mother–child dyads enrolled in the Study to Explore Early Development (2007–2020), a US multisite case–control study. Receipt of LEA during childbirth and other covariate information was ascertained from a combination of maternal self‐report, medical record abstraction, and the birth certificate. ASD classification was determined by trained psychologists using the Autism Diagnostic Observation Schedule and Autism Diagnostic Interview‐Revised. We used logistic regression to estimate the odds ratio (OR) for the association between LEA and ASD in offspring. Models were adjusted for demographic and pregnancy factors. Sensitivity analyses restricted to term deliveries, singleton pregnancies, and vaginal births were conducted. Our sample included 2039 ASD cases and 3171 controls. The prevalence of LEA use was similar among cases and controls (66% and 67%, respectively). The crude OR for the association between LEA and ASD was 0.97 (95% CI: 0.85, 1.10), and the adjusted OR was 1.02 (95% CI: 0.89, 1.17). Findings from sensitivity analyses were generally consistent with the primary results. Subtle associations emerged when the analysis was restricted to vaginal deliveries; however, they attenuated after additional adjustment for fetal distress, induced or augmented labor, and prolonged labor. Our findings do not support an association between LEA and ASD in offspring.\n"]