The authors tested the hypothesis that the birth prevalence of gastroschisis is positively associated with use of recreational drugs in early pregnancy. A matched case-control study was carried out in three regions of the United Kingdom over the period January 2001 through August 2003. For each case, three liveborn controls were matched by initial intended place of delivery, region, and maternal age. Maternal hair analysis provided independent verification of recreational drug use. Conditional logistic regression was used to estimate mutually adjusted odds ratios. Estimates were revised using data from hair analysis. Statistically significant adjusted odds ratios for gastroschisis were associated with first-trimester use of 1) any recreational drug (odds ratio (OR) = 2.2, 95% confidence interval (CI): 1.2, 4.3) and 2) vasoconstrictive recreational drugs (defined as cocaine, amphetamines, and ecstasy) (OR = 3.3, 95% CI: 1.0, 10.5). Other significant exposures included aspirin use (OR = 20.4, 95% CI: 2.2, 191.5), cigarette smoking (OR = 1.7, 95% CI: 1.1, 2.6), and prior history of gynecologic infection/disease (OR = 2.6, 95% CI: 1.2, 5.6). Recreational drug use is a significant risk factor for gastroschisis and is one of a constellation of potentially preventable exposures which include cigarette smoking, aspirin use, and history of gynecologic infection/disease. Maternal hair analysis proved an acceptable and valuable method of independently verifying recreational drug use.