CONTEXT: The association between acid-suppressive drug exposure during pregnancy and childhood asthma has not been well established. OBJECTIVE: To conduct a systematic review and meta-analysis on this association to provide further justification for the current studies. DATA SOURCES: We searched PubMed, Medline, Embase, the Cochrane Database of Systematic Reviews, EBSCO Information Services, Web of Science, and Google Scholar from inception until June 2017. STUDY SELECTION: Observational studies in which researchers assessed acid-suppressive drug use during pregnancy and the risk of childhood asthma were included. DATA EXTRACTION: Of 556 screened articles, 8 population-based studies were included in the final analyses. RESULTS: When all the studies were pooled, acid-suppressive drug use in pregnancy was associated with an increased risk of asthma in childhood (relative risk [RR] = 1.45; 95% confidence interval [CI] 1.35-1.56; I-2 = 0%; P <.00001). The overall risk of asthma in childhood increased among proton pump inhibitor users (RR = 1.34; 95% CI 1.18-1.52; I-2 = 46%; P <.00001) and histamine-2 receptor antagonist users (RR = 1.57; 95% CI 1.46-1.69; I-2 = 0%; P <.00001). LIMITATIONS: None of the researchers in the studies in this meta-analysis adjusted for the full panel of known confounders in these associations. CONCLUSIONS: The evidence suggests that prenatal, maternal, acid-suppressive drug use is associated with an increased risk of childhood asthma. This information may help clinicians and parents to use caution when deciding whether to take acid-suppressing drugs during pregnancy because of the risk of asthma in offspring.