Nausea and vomiting after esophagogastroduodenoscopy have not been studied in detail. The aim of this study was to evaluate the risk factors for post-endoscopic nausea. We performed a case-control study at the Toyoshima Endoscopy Clinic. Eighteen patients with post-endoscopic nausea and 190 controls without post-endoscopic nausea were analyzed. We conducted univariate and multivariate logistic regression analyses with respect to patient age; sex; body height; body weight; the use of psychotropic drugs as baseline medications; and the dosing amounts of midazolam, pethidine, flumazenil and naloxone. On univariate analysis, post-endoscopic nausea was significantly related with patient age (odds ratio = 0.946); female sex (odds ratio = 10.85); body weight (odds ratio = 0.975); and the dose per kg body weight of pethidine (odds ratio = 53.03), naloxone (odds ratio = 1.676), and flumazenil (odds ratio = 1.26). On multivariate analysis, the dose per kg body weight of pethidine (odds ratio = 21.67, p = 0.004) and female sex (odds ratio = 13.12, p = 0.047) were the factors independently associated with post-endoscopic nausea. The prevalence of nausea after esophagogastroduodenoscopy was 0.49% (18/3,654). In conclusion, post-endoscopic nausea was associated with the dose of pethidine and female sex.