Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed to pregnant women. Therefore, research on in utero exposure to SSRIs can be helpful in informing patients and clinicians. The aim of this retrospective two-cohort study was to determine whether there is a statistically significant increase in Chiari I malformations (CIM) in children exposed to SSRIs during pregnancy. A total of 33 children whose mothers received a diagnosis of depression and took SSRIs during pregnancy (SSRI-exposed cohort) were matched to 66 children with no history of maternal depression and no SSRI exposure. In addition, 30 children whose mothers received a diagnosis of depression, but did not receive antidepressants during pregnancy (history of maternal depression cohort), were matched to 60 children with no history of maternal depression and no SSRI exposure. Main outcome was presence/absence of CIM on MRI scans at 1 and/or 2 years of age. Scans were reviewed by two independent neuroradiologists who were blind to exposure status. The SSRI-exposed children were significantly more likely to be classified as CIM than comparison children with no history of maternal depression and no SSRI exposure (18% vs 2%, p=0.003, OR estimate 10.32, 95% Wald confidence limits 2.04-102.46). Duration of SSRI exposure, SSRI exposure at conception, and family history of depression increased the risk. The history of maternal depression cohort did not differ from comparison children with no history of maternal depression and no SSRI exposure in occurrence of CIM (7% vs 5%, p=0.75, OR estimate 1.44, 95% Wald confidence limits 0.23-7.85). Replication is needed, as is additional research to clarify whether SSRIs directly impact risk for CIM or whether this relationship is mediated by severity of depressive symptoms during pregnancy. We would discourage clinicians from altering their prescribing practices until such research is available.