Background: Gastroschisis, a congenital anomaly involving a defect in the fetal abdominal wall, has increased in prevalence in many countries, but the aetiology is uncertain. We tested the hypothesis that high maternal alcohol consumption and poor diet in the first trimester are risk factors in a case?control study in the UK (1 July 2007 to 28 February 2010). Methods: Gastroschisis cases and three controls per case (matched for maternal age) were identified at 18- to 20-week routine anomaly screening ultrasound scan (USS). Interviews were carried out during the antenatal period (median 24 weeks' gestation) using a piloted questionnaire. Conditional logistic regression was used to describe the associations between exposure variables and gastroschisis, adjusted for known confounding variables. Results: The response rate was 73% for cases (n?=?91) and 70% for controls (n?=?217). High consumption of fruits and vegetables during the first trimester (aOR 0.2; 95% CI 0.04?0.6), taking folic acid for at least 6 weeks during the first trimester (aOR 0.3; 95% CI 0.1?0.7) and increasing body fat percentage of total maternal body weight (aOR 0.9; 95% CI 0.8?0.9 per 1% increase) were independently associated with reduced risk. Cigarette smoking (aOR 2.7; 95% CI 1.1?6.8) was an independent risk factor. Conclusion: We report for the first time that higher intake of fruits and vegetables during the first trimester, longer duration of folic acid supplementation and higher body fat percentage are associated with reduced risk of fetal gastroschisis, independent of cigarette smoking. The increased risk of cigarette smoking is greatest in older women and in high socio-economic groups.