Polyethylene glycol (PEG) is considered the gold standard regimen for bowel preparation; however, due to the necessity of a large volume, patient tolerance is impaired. Therefore, lactulose is a novel alternative for colonoscopy preparation. This study aimed to investigate the efficacy and safety of lactulose-based bowel preparations in comparison with PEG for colonoscopy. This is a prospective, non-blinded, comparative study. Outpatients were randomly divided into two groups: group 1 (111 patients), PEG; and group 2 (111 patients), lactulose. The following clinical outcomes were assessed in each group: degree of bowel clearance using the Boston bowel preparation score, colorectal polyp detection rate, adenoma detection rate, tolerability, and side effects. The rate of inadequate bowel preparation was 8.1% and 1.8% for the PEG and lactulose groups, respectively (p=0.030). The Boston bowel preparation score for the entire colon was 7.34±1.17 and 8.36±1.09 for the PEG and lactulose groups, respectively (p<0.001). The satisfactory overall experience rates were 27.9% and 62.2% for the PEG and lactulose groups, respectively (p<0.001). The novel bowel preparation with oral lactulose was superior to that with PEG in terms of colon cleansing, adenoma detection rate, tolerance, and patient experience.