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Substance use during pregnancy is associated with adverse pregnancy and neonatal outcomes; eHealth interventions offer a potential accessible treatment option. The objective of this systematic review and meta-analysis was to evaluate the effectiveness of eHealth interventions for the treatment of substance use during pregnancy. A comprehensive search of PsycINFO, Medline, CINAHL, Cochrane and Embase databases was conducted from May 2020 to April 2021. The protocol for this study was registered with Prospero (CRD42020205186) through the University of York Centre for Reviews and Dissemination. Two independent reviewers completed screening, data extraction, and quality assessment. RCTs were included if they reported: (a) administration of an eHealth intervention for (b) substance use outcomes, among (c) pregnant individuals. Comprehensive Meta-Analysis Software (CMA) was used to calculate pooled effect sizes (Odds Ratio) to determine the effect of eHealth interventions on substance use outcomes. Six studies were identified with substance use outcomes that included: smoking ( n = 3), alcohol ( n = 2), and other ( n = 1). eHealth interventions were delivered through the internet ( n = 1), computer ( n = 3), telephone ( n = 1), and text ( n = 1). Results suggested that eHealth interventions significantly reduced substance use in pregnant individuals compared to controls (OR = 1.33, 95% CI = 1.06 to 1.65, p = 0.013). eHealth interventions offer a promising and accessible treatment option to reduce substance use during pregnancy. This work was supported by the generous donors of the Alberta Children's Hospital Foundation, the Canadian Child Health Clinician Scientist Program (CCHCSP), the Canadian Institute of Health Research and the Fonds de Recherche du Québec-Santé.