Obesity is a disease which is increasing in prevalence among US adults. There is a minimal amount of research focused on the safety of moderate sedation for endoscopic procedures among obese patients (BMI > 30) with some suggestions that obese patients are at increased risk of complications and should be sedated with Anesthesia assistance. There is no published data on the sedation of super obese patients (BMI ≥ 50). The aim of our study was to evaluate the safety of moderate sedation and endoscopic procedural outcomes for super obese patients in a case control study. We completed an age and sex matched case control study, comparing 132 super obese patients (BMI ≥ 50) to 132 non-obese controls, evaluating the risks of general endoscopic procedures (upper endoscopy and colonoscopy) completed with moderate sedation (intravenous fentanyl, midazolam and prn diphenhydramine). We assessed procedure completion rates, intra-procedure complications, delayed complications (occurring within 30 days of the procedure), doses of sedation medication used and procedure durations. The mean age of the cases and controls was 54, SD ± 9.9, 65 % female. 114 colonoscopies, 17 EGD/colonoscopies and 1 EGD were compared for each group. There was no difference in age, gender, nor procedure type between the case and control subjects. The mean BMI for the super obese cohort was 55.6 compared to 22.5 for the controls (P < 0.001). The American Society of Anesthesiologists (ASA) classification was significantly higher for the obese patients compared to the controls, 1.9 vs 1.5 (P < 0.001). The mean intra-procedure fentanyl dose and midazolam dose was significantly higher for the obese patients compared to the controls, fentanyl 180 mcg and midazolam 7.7 mg vs fentanyl 148 mcg and midazolam 6.4 mg respectively, (P < 0.001, P < 0.001). The percent of patients given adjunct IV diphenhydramine was significantly higher for the obese cohort, 53 %, compared to the control patients, 7 %, (P < 0.001). Procedure completion rates were 100 % for both cases and controls. There was no significant difference in the procedure duration for the obese patients compared to controls, 24.6 min. vs 22.6 min. (P = 0.09). There was a significantly higher percent of brief intra-procedure hypoxia (Oxygen blood saturation < 90%) for the obese patients compared to the controls, 5 % vs 0 %, (P = 0.02). 2 % of the cases and 2 % of the controls had delayed complications (P = 1.0). 1) General endoscopic procedures can be safely and effectively performed in super obese patients, defined as BMI ≥ 50, with moderate sedation. 2) Brief intra-procedure hypoxia more commonly occurs in super obese patients and higher medication doses are required.