Introduction: Dimethicone enhances diagnostic accuracy in Oesophagogastroduodenoscopy (EGD). Various regimens have been tried to ease the procedure for better mucosal visibility. Aim: To evaluate the efficacy of activated dimethicone in improving endoscopic visibility. Materials and Methods: The present prospective study was carried out from February 2017 to February 2018 in a tertiary teaching hospital, Chennai, India. A total of 2917 patients aged 18-70 years were enrolled for this study. The participants were divided into group S (1540 patients) and group C (1377 patients). Group S received activated dimethicone 30 minutes before the procedure and group C underwent procedure without any pre-procedure preparation. The mucosal visibility score was evaluated in both the groups. Statistical analysis was conducted using IBM SPSS statistics (version 23.0). Unpaired student’s t-test and Pearson Chi-Square test are used for statistical analysis of the data and in both, p<0.05 was considered as significant level. Results: The mucosal visibility score in oesophagus, stomach, antrum and duodenum was significantly better in group S patients compared to group C patients. Duration of endoscopy was significantly (p-value 0.0005) shorter (7.95 min) in the group S compared with the group C (8.17 min). The amount of flush used was on an average 3 mL less for group S than group C, which was also significant (p-value 0.0005). Conclusion: Activated dimethicone pre-preparation to EGD significantly increased the mucosal visibility during procedure and decreased the endoscopy duration.