Initially introduced as a safer alternative to smoking, electronic cigarettes (e-cigarettes) and vaping have since been associated with lung injury. Nevertheless, there is limited perioperative data on their potential contribution to the harmful effects of mechanical ventilation on the lungs. We hypothesized that, in adults undergoing noncardiothoracic surgeries, preoperative vaping/e-cigarette use is associated with hypoxemia during the first postoperative hour, and with an increased incidence of intraoperative and postoperative pulmonary complications. We conducted a retrospective cohort study in which we included patients reporting as vapers/e-cigarette users within one year before surgery as the exposure group, and nonvapers as the control group. The primary outcome was the time-weighted average (TWA) SpO2/FIO2 ratio in the postanesthesia care unit during the first postoperative hour. The secondary outcome was a composite of intraoperative and postoperative pulmonary complications until discharge. We used entropy balancing to adjust for confounding, and fit weighted linear regression and logistic regression models to estimate treatment effects. A total of 110,940 patients met the inclusion criteria, and 1,941 of these were vapers/e-cigarette users. The average treatment effect on the treated for TWA SpO2/FIO2 ratio (N = 109,217) was estimated to be a mean difference of 4 (95% confidence interval [CI], 1 to 8; P = 0.007). This is equivalent to a 4% change in SpO2 at a 30% FIO2 (or at a fixed FIO2). The difference was statistically significant. The average treatment effect on the treated for experiencing intraoperative and postoperative pulmonary complications (N = 110,940) was an odds ratio of 1.04 (95% CI, 0.71 to 1.54; P = 0.84). Vaping/e-cigarette use was neither associated with clinically significant hypoxemia during the first hour in the postanesthesia care unit nor with an increase in pulmonary complications. Nevertheless, our findings cannot definitively exclude the deleterious effects of vaping and e-cigarette use on the lungs, and anesthesiologists should consider potential perioperative complications.