Abstract Background As prenatal vaccinations continue to be given more frequently, it is important to assess long-term safety events. We investigated the association between prenatal influenza vaccination or infection and autism spectrum disorder (ASD) in offspring. Methods A retrospective cohort study of mother–child pairs with deliveries between 1 January 2011 and 31 December 2014 at Kaiser Permanente Southern California was performed. Children aged >1 year were followed through 31 December 2018. Maternal influenza vaccination or infection during pregnancy was obtained from electronic health records. ASD was defined by International Classification of Diseases, Ninth or Tenth Revisions, Clinical Modification, codes after age 1 year. Cox proportional hazard models estimated the crude and inverse probability of treatment weighted (IPTW) hazard ratios (HR) for the association between maternal influenza vaccination or infection and ASD. Results There were 84 739 mother–child pairs included in the final analytic sample. Of the 46 257 women vaccinated, 32.4% were vaccinated during the first trimester, 41.8% during the second trimester, and 25.8% during the third trimester. ASD was diagnosed in 1930 (2.3%) children. The IPTW analyses showed no association between prenatal influenza vaccination or infection and ASD in offspring (HR, 1.04; 95% confidence interval [CI], .95–1.13; HR, 1.12; 95% CI, .66–1.89, respectively). Conclusions Prenatal influenza vaccination or infection was not associated with ASD risk in offspring. The findings support recommendations to vaccinate pregnant women to protect themselves and their infants, both of whom are vulnerable to severe morbidity following infection.