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Abstract Although electronic cigarette (e-cigarette) aerosol contains similar toxicants to combustible cigarettes, few studies have examined their influence on fecundability. We assessed the association between e-cigarette use and fecundability, overall and according to combustible cigarette smoking history, in a cohort of 4,586 North American women (aged 21–45 years) enrolled during 2017–2020 in Pregnancy Study Online, a Web-based prospective preconception study. Women reported current and former e-cigarette use on baseline and follow-up questionnaires, and they completed bimonthly follow-up questionnaires until self-reported pregnancy or censoring. Fecundability ratios and 95% confidence intervals were calculated using proportional probabilities models, controlling for potential confounders. Overall, 17% of women had ever used e-cigarettes and 4% were current users. Compared with never use of e-cigarettes, current e-cigarette use was associated with slightly lower fecundability (fecundability ratio = 0.84, 95% confidence interval (CI): 0.67, 1.06). Compared with current nonusers of e-cigarettes and combustible cigarettes, fecundability ratios were 0.83 (95% CI: 0.54, 1.29) for current dual users of e-cigarettes and combustible cigarettes, 0.91 (95% CI: 0.70, 1.18) for current e-cigarette users who were nonsmokers of combustible cigarettes, and 1.01 (95% CI: 0.85, 1.20) for nonusers of e-cigarettes who were current smokers of combustible cigarettes. Current e-cigarette use was associated with slightly reduced fecundability, but estimates of its independent and joint associations with combustible cigarette smoking were inconsistent and imprecise.