We investigated the role of maternal environmental factors in the aetiology of congenital heart disease (CHD). A population-based case-control study (242 CHD cases, 966 controls) was conducted using an iPad questionnaire for mother with linkage to maternity and first trimester prescription records. Risk of CHD was associated with low maternal education (OR adjusted for confounders 1.59; 95% confidence interval [CI], 1.02–2.49), pregestational diabetes (OR 4.04; 95% CI 1.00–16.28), self-reported maternal clotting disorders (adjOR 8.55, 95%CI 1.51–48.44), prescriptions for the anticlotting medication enoxaparin (adjOR 3.22, 95%CI 1.01–10.22) and self-reported vaginal infections (adjOR 1.69, 95%CI 1.01–2.80). There was no strong support for the hypothesis that periconceptional folic acid supplements have a protective effect, but there was a protective effect of frequent consumption of folate rich fruits (adjOR 0.64, 95%CI 0.47–0.89). Compared to the most common pre-pregnancy dietary pattern, CHD risk was associated with a poor diet low in fruit and vegetables (adjOR 1.56, 95%CI 1.05–2.34). Mothers of cases reported more pregnancy related stress (adjOR 1.69; 95% CI 1.22–2.34) and multiple stressors (adjOR 1.94, 95%CI 0.83–4.53). We found no supportive evidence for CHD risk being associated with obesity, smoking, depression or antidepressant use in this population. Our findings add to the previous evidence base to show potential for public health approaches to help prevent CHD in future by modifying environmental factors. Independent confirmation should be sought regarding elevated CHD risk associated with maternal blood clotting disorders and their treatment, since we are the first to report this.