Background and Aim: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits. Patients with IBS requiring colonoscopy take longer time to cecum with higher need for medications used for conscious sedation. Glucagon is routinely used during endoscopic procedures to reduce peristalsis that interfere with the procedure. However, randomized controlled data using glucagon during endoscopic procedures are lacking. We designed a prospective randomized placebo-controlled trial to study the effect of intravenous glucagon given during colonoscopy. Materials and Methods: We received approval from the FDA for this off-label use of glucagon during colonoscopy. This is a double-blind randomized placebo-controlled study. Patients were selected based on ROME III criteria for IBS; patients who met Rome III criteria and had an indication for colonoscopy for age-specific colon cancer screening or for work up of any alarm signs. We selected 34 patients meeting the Rome III for IBS and randomized into Group A and Group B. Both the performing endoscopist and patients were blinded. These patients in both groups initially received a standard dose of conscious sedation, up to 100 mcg of fentanyl and up to 5 mg of midazolam intravenously. In Group A, 17 patients, in addition to conscious sedation, received 1 ml saline as placebo. In Group B, 17 patients, in addition to conscious sedation, received 1 mg of intravenous glucagon. Parameters evaluated were as follows: 1) Total time required for colonoscopy 2) Completion of colonoscopy as documented by cecal intubation or visualization of appendicular orifice 3) Level of comfort in patient concerned to postprocedure spasmodic pain, which was based on Wong-Baker FACES pain rating scale and 4) Calculate the amount of sedation required in both groups of patients and also at what extent glucagon helped to decrease the requirement of sedatives. Data was analyzed using the student t-test.