Approximately half of all women suffer from heartburn at some stage during pregnancy. The most effective treatment is proton pump inhibitors, but the safety of use during pregnancy cannot be guaranteed. This study aimed to elucidate the effect of proton pump inhibitors on the risk of pre-eclampsia, gestational diabetes mellitus, preterm birth, an Apgar score at 5 min below 7, and a child being small or large for its gestational age. This Swedish population-based study included 1,089,514 live singleton deliveries between July 2006 and December 2016 in Sweden. Multiple logistic regression was used to model the outcomes as a function of the covariates. Results were presented as odds ratios with 95% confidence intervals. In 1.4% of all pregnancies, the mother used proton pump inhibitors in the period from 3 months before the last menstrual period up to delivery. The use of proton pump inhibitors was associated with higher odds of pre-eclampsia (odds ratio = 1.