Gastroschisis is a congenital defect of the abdominal wall that occurs most commonly in the offspring of young women. The defect is often hypothesized to result from vascular disruption in the early embryo. We measured the associations between maternal vasoactive exposures in pregnancy, as possible markers of vascular disruption, and gastroschisis risk, using data collected as part of the National Birth Defects Prevention Study. Study participants included mothers of births from October 1997 to December 2003 in 10 states. The mothers of 514 gastroschisis cases were matched by age at delivery and state to 3,277 non-malformed controls and compared for periconceptional smoking and use of vasoconstrictors, non-steroidal anti-inflammatory drugs (NSAIDs), and vasodilators. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) were estimated from conditional logistic regression. Case mothers were more likely than control mothers to smoke (OR = 1.5, 95% CI = 1.2–1.9) and report use of non-aspirin NSAIDs (1.4, 1.1–1.7) and anti-hypertensive vasodilators (2.6, 0.9–8.0), but not vasoconstrictive decongestants (1.0, 0.7–1.4). Cigarette smoking had little effect on gastroschisis risk in mothers <25 years of age, but the OR was 3.0 (1.8–5.0) for those ≥25 years. Likewise, ORs were greatest in the older women for use of non-aspirin NSAIDs (1.6, 1.0–2.6) and bronchodilators (3.0, 1.8–5.0). These findings suggest that, overall, vasoactive risk factors play a minor role in the etiology of gastroschisis, and do not support the vascular disruption hypothesis. However, the observation that increased ORs for some vasoactive exposures were confined to older women raises the question of whether inherent maternal factors might influence risk. © 2009 Wiley-Liss, Inc.