BackgroundObesity is a risk factor for sedation-related respiratory depression during colonoscopy. In a colonoscopy, propofol is frequently used because of its strong sedative and hypnotic properties. However, propofol is associated with marked respiratory depression. The objective of this trial was to investigate the effectiveness and safety of dexmedetomidine plus oxycodone for conscious sedation during colonoscopy in obese patients. MethodsA total of 120 patients had colonoscopies, and they were divided into two groups at random: Dexmedetomidine and oxycodone were used to sedate group Dex + oxy; while group Pro + oxy received anesthesia with propofol plus oxycodone. Parameters including blood pressure, heart rate, respiration, blood oxygen saturation, injection pain, and recovery time were recorded for both groups. ResultsThe incidence of hypoxemia was significantly reduced in group Dex + oxy compared with group Pro + oxy (4.9% vs 20.3%, P = 0.011). Blood pressure was lower, and heart rate was higher in group Pro + oxy compared with group Dex + oxy (P < 0.05). In addition, group Dex + oxy showed a significantly shorter caecal insertion time, recovery time to orientation, and recovery time to walking than group Pro + oxy (P < 0.05). Endoscopist satisfaction scores were significantly higher in group Dex + oxy compared with group Pro + oxy (P = 0.042). ConclusionFor obese patients, dexmedetomidine plus oxycodone effectively sedate them with few adverse effects, while also reducing colonoscopy operation difficulty by allowing obese patients to reposition. Thus, dexmedetomidine plus oxycodone could be used safely as a conscious sedation method for colonoscopy in obese patients. Trial registrationThe protocol was registered at www.chictr.org.cn (ChiCTR1800017283, July 21, 2018).