BACKGROUND: We assessed the effects and safety of aspirin treatment during pregnancy on fetal and neonatal outcomes. METHODS: We searched MEDLINE (1966–2001), EMBASE (1980–2000), TOXLINE (1994–2000), EBM Cochrane Database of Systematic Reviews (1991–2000), Reproductive Toxicology (2001), teratology texts, and bibliographies of all the included studies. We looked for published randomized controlled studies reporting aspirin treatment to improve outcomes of moderate- and high-risk pregnancies. The key words used to search for articles about exposure to aspirin were salicylic acid, pregnancy, and pregnancy complications; key words used to search for outcome were neonatal diseases and abnormalities. Based on our search strategy, 1904 citations were identified; their titles and abstracts were reviewed by one reviewer. Of these citations, 182 papers were selected for detailed review. Two reviewers independently determined whether a study should be included in the final analysis. In cases of disagreement, the decision was based on the assessment of a third reviewer. RESULTS: Data were extracted independently by each reviewer. We calculated the pooled relative risk (RR) or weighted mean difference and 95% confidence intervals (CI), assuming a random-effect model. Thirty-eight studies met the inclusion criteria. The risk for miscarriage did not differ between women treated with aspirin and placebo (seven studies; RR, 0.92; 95% CI, 0.71–119). Women who took aspirin had a significantly lower risk of preterm delivery than did those treated with placebo (22 studies; RR, 0.92; 95% CI, 0.86–0.98). There was no significant difference in perinatal mortality (20 studies; RR, 0.92; 95% CI, 0.81–1.05) and in the rate of small-for-gestational-age infants (12 studies; RR, 0.96; 95% CI, 0.87–1.07) among offspring of mothers treated with aspirin and those of mothers treated with a placebo. CONCLUSION: For women with moderate- and high-risk pregnancies, aspirin treatment seemed to have a small but significant effect on reducing the rate of preterm deliveries, but did not reduce the rate of perinatal death. Birth Defects Research (Part B) 68:70–84, 2003. © 2003 Wiley-Liss, Inc.