Aims and method: To examine the association between the use of paroxetine during pregnancy and the risk of cardiovascular defects in the newborn. A systematic review of nine electronic databases was carried out and bibliographies were hand-searched for other relevant articles. Inclusion criteria for studies were the use of selective serotonin reuptake inhibitors in the first trimester of pregnancy, with separate data available for paroxetine and cardiovascular defects in newborn babies. A random-effect model was used to combine the data. Results: A total of 11 studies were included in the analysis, concerning 4515 offspring who were exposed to paroxetine in the first trimester and 1 469 302 controls. In pooled analysis, paroxetine in the first trimester of pregnancy was slightly, but significantly, associated with a risk of cardiovascular malformations in the offspring (relative risk = 1.25, 95% CI 1.01-1.54). Separate analyses of case-control and cohort studies made this difference non-significant. Clinical implications: This meta-analysis supports current guidelines advising not to use paroxetine in early pregnancy.