The aim of our systematic review and meta-analysis was to evaluate the risk of neural tube defects (NTDs) according to the pre-pregnancy body mass index. Electronic databases were searched (MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library). Selection criteria included prospective and retrospective cohort studies reporting the prevalence of fetal NTDs in obese, overweight, and underweight pregnant women. Odds ratios (ORs) comparing risk among these subsets of pregnancies with normal weight mothers were determined with 95% confidence intervals (CI). The evaluated outcome was the association between maternal underweight, overweight, and obesity and the risk of NTDs. We included ten studies published between 2000 and 2017, including underweight, overweight, and obese pregnant women with fetal NTD (cases) and pregnant women with recommended BMI with fetal NTD (controls). Compared with normal BMI women, obese mothers were at significantly higher risk of fetal NTDs (0.53 vs. 0.33%; OR 1.62 95% CI 1.32–1.99, p < .0001), while no difference for the risk of NTDs was found when comparing overweight (0.34 vs. 0.32%; OR 1.09 95% CI 0.92–1.3, p = .3) and underweight (0.65 vs. 0.24%; OR 1.34 95% CI 0.73–2.47, p = .34) with normal weight pregnant women. Obese pregnant women are at significantly higher risk NTDs, while no significant difference has been found in overweight and underweight pregnant women. Key message Obese pregnant women are at significantly higher risk of NTDs, such as spina bifida compared with normal weight women. No difference was found when comparing overweight and underweight with normal weight women. Obese pregnant women are at significantly higher risk of NTDs, such as spina bifida compared with normal weight women. No difference was found when comparing overweight and underweight with normal weight women.