Marijuana usage has increased significantly as it has become more readily available and legal, either recreationally or medicinally, in many states. It has been postulated that marijuana usage increases the amount of sedation required for procedures. However, there are minimal data defining this relationship. We aimed to establish the relationship between marijuana usage and the amount of sedation used during endoscopy.This was a single-institution prospective study of patients undergoing outpatient endoscopy (both monitored anesthesia care [MAC] and moderate sedation) at the Oklahoma City Veterans Affairs Medical Center. Marijuana usage was assessed by a voluntary de-identified pre-endoscopy survey. Information regarding sedation used, endoscopy outcomes, demographics, comorbidities, medical history, and medications used was extracted from the medical record. A univariate and stratified analysis of alcohol usage was performed. A P value of <.05 was considered to be significant.A total of 976 patients were analyzed; 21.5% of them endorsed marijuana usage (210/976). Marijuana users were found to be younger (P = .0002), leaner (P < .0001), and less likely to have diabetes (P = .002), obstructive sleep apnea (P = .0002), and hypertension (P = .04). They were also more likely to smoke (P < .0001) and vape (P < .0001). Marijuana usage was associated with a higher requirement of sedation (fentanyl [P = .003], midazolam [P = .05], propofol [P = .02]) and higher use of adjunct sedation (diphenhydramine in moderate sedation [P = .0003]). Further multivariate analyses were performed to control for possible confounders. Marijuana usage was still deemed to be an independent predictor for high propofol use among MAC cases (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.00-3.12). Likewise, marijuana usage was found to be an independent predictor for high midazolam use (OR, 1.57; 95% CI, 1.02-2.42) and high fentanyl use (OR, 1.54; 95% CI, 0.98-2.38), but failed to reach statistical significance in the fentanyl group.Marijuana use is associated with a significantly higher amount of sedation along with a significantly higher usage of other adjunct sedatives. A patient's marijuana history should be considered when determining the methods of sedation to be used for endoscopy.