Background: Colorectal cancer (CRC) is the third most prevalent cancer in the world. Preparation for a colonoscopy, the gold standard in screening for CRC, has been done with different methods. The use of opioids may cause inadequate colonic preparation. This study’s aim was to compare the quality of bowel preparation using split doses versus the same-day dose of polyethylene glycol (PEG) in opiate-dependent non-addicted patients in a tertiary care center, Northeast of Iran. Methods: The present study is a randomized double-blind controlled trial study (IRCT20180103038196N6). Two groups of 100 opiate-dependent patients each referred for screening colonoscopy were enrolled in the study during 2017. Subjects were randomized to receive split-dose or the same-day dose of PEG. The quality of bowel preparation was assessed using the Ottawa Bowel Preparation Scale. Results: In this clinical trial, opiate-dependent patients that were candidates for colonoscopy were enrolled with mean age of 56.21 (12.34) years in split-dose group and 53.85 (13.45) years in same-day dose group. Results showed that the Ottawa score was significantly lower (better results) in the split-dose group than the same-day dose group and the preparedness was better in right and mid-colon areas (3.05 vs. 3.83, P = 0.022, 0.72 vs. 1.12, P=0.003, 0.52 vs. 0.79, P=0.035 respectively). But in the rectosigmoid colon, the Ottawa score was lower (better results) in the same-day dose group than in the split-dose group (P = 0.020). The total Ottawa score was also lower in the split-dose (P = 0.022), which means better preparation in the split-dose group Conclusion: The split-dose preparation is better than the conventional previous evening preparation in terms of bowel preparation quality and patient compliance.