Colonoscopy is the gold standard investigation for large bowel disease. With the increase in demand, pressure is on clinics to shorten lengths of time per procedure in addition to maintaining high levels of patient safety. Analgesia has always been the mainstay of adequate pain relief, but it leads to prolonged recovery and lengths of hospital stay, in addition to increased risk of cardio-respiratory side effects. N2O/O2 mixtures have been used for its effective analgesic effect and short half life and provides an alternative method of sedation for colonoscopy procedures.The primary objective was to compare the overall effectiveness of nitrous oxide mixtures to other types of pain relief used during colonoscopy procedures to provide adequate pain/discomfort relief.The secondary objective was to compare between nitrous oxide and other types of pain relief with respect to hospitalisation/recovery time, side effects, patients and endoscopists satisfaction, and colonoscopy completion rates.The following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE (1966- present), EMBASE (1980 - present), and the Internet (Google Scholar).Randomised controlled trials which compared nitrous oxide to placebo or active comparators for patients undergoing elective colonoscopic procedures. Patients with known underlying causes of pain/discomfort were excluded. Seven randomised trials were included. Each trial compared a nitrous oxide/oxygen mixture to a placebo or sedation +- other analgesic drugs on patients undergoing elective colonoscopic procedures. The results of these studies were analysed and discussed.There were a total of 547 patients included.There were 257 patients randomised to receive the N2O/O2 mixture (7 studies), while 225 patients received some form of sedation with or without other analgesia (6 studies), and 65 patients received a placebo (3 studies).Four studies showed that N2O/O2 is as good in controlling pain/discomfort as conventional methods, while one showed sedation was better and another study showed N2O/O2 was better.Six of the studies showed that N2O/O2 groups had quicker recovery times and shorter lengths of hospital stays while one study showed that there was no difference between the two groups.Two studies showed that N2O/O2 was safer while one reported that sedation was safer.Nitrous oxide is as efficient and safer than various pain relief methods used during colonoscopy procedures, but further trials are necessary.