Of 110,783 pregnancies during 1998–2009 in southern Israel, 5,267 mothers were exposed to NSAIDs (nonselective cyclooxygenase [COX] and selective COX2 inhibitors) during their first trimester. Intrauterine exposure to NSAIDs did not increase the risk of major congenital malformations in general; however, exposure to selective COX2 inhibitors was associated with an increased risk of musculoskeletal malformations (adjusted OR 3.39; 95% CI 1.37–8.34).