Mucosal visibility during gastroscopy can be impaired by mucus, bilis, bubbles and saliva. It also can increase the duration and the difficulty of the procedure, with a potential increase in discomfort for the patient. Evaluate the efficacy and safety of premedication with Dimethicone, N-Acetylcysteine and Pancreatin during upper digestive endoscopy. Randomized, double-blind, controlled trial at a National referral center in Mexico. From May to September 2019, 163 patients who underwent routine gastroscopy were recruited. They were randomized 1:1:1 to receive premedication with 100ml of water (Group A); 100ml of water, 100mg of Dimethicone and 600mg of N-Acetylcisteine (Group B); or, 100ml of water, 100mg of Dimethicone, 600mg of N-Acetylcisteine and 300mg of Pancreatin (Group C). Endoscopists and patients were blinded to group allocation. Mucosal visibility was evaluated by 3 experienced endoscopists in the lower esophagus, the stomach (fundus, body, antrum), and in the duodenum. A 3-point previously validated scale was used (1=worst, 3=best). The primary outcome was mucosal visibility. Secondary outcomes were intragastric volume, volume of fluid required to achieve adequate visibility, procedure duration, tolerance, and adverse events. Analysis was done with Kruskal-Wallis test and U Mann-Whitney (Stata v13, p<0.05). Mean mucosal visibility score, mean flush volume required to achieve adequate mucosa views and procedure duration for Group B and C was better than for Group A (Table 1) in lower esophagus, stomach, and duodenum (p 0.0001). No difference was found in intragastric volume between any of the 3 groups (p 0.13). No adverse events were reported, and the three groups experienced good tolerance for the premedication. Premedication with Dimethicone and N-acetylcisteine significantly improves mucosal visibility during gastroscopy. Furthermore, it reduces mean flush volume required to achieve adequate mucosal visibility and procedure duration when compared to placebo.