BACKGROUND The incidence and mortality rate of colorectal cancer progressively increase with age and become particularly prominent after the age of 50 years. Therefore, the population that is >= 50 years in age requires long-term and regular colonoscopies. Uncomfortable bowel preparation is the main reason preventing patients from undergoing regular colonoscopies. The standard bowel preparation regimen of 4-L polyethylene glycol (PEG) is effective but poorly tolerated. AIM To investigate an effective and comfortable bowel preparation regimen for hospitalized patients >= 50 years in age. METHODS Patients were randomly assigned to group 1 (2-L PEG + 30-mL lactulose + a low-residue diet) or group 2 (4-L PEG). Adequate bowel preparation was defined as a Boston bowel preparation scale (BBPS) score of >= 6, with a score of >= 2 for each segment. Non-inferiority was prespecified with a margin of 10%. Additionally, the degree of comfort was assessed based on the comfort questionnaire. RESULTS The proportion of patients with a BBPS score of >= 6 in group 1 was not significantly different from that in group 2, as demonstrated by intention-to-treat (91.2% vs 91.0%, P = 0.953) and per-protocol (91.8% vs 91.0%, P = 0.802) analyses. Furthermore, in patients >= 75 years in age, the proportion of BBPS scores of >= 6 in group 1 was not significantly different from that in group 2 (90.9% vs 97.0%, P = 0.716). Group 1 had higher comfort scores (8.85 +/- 1.162 vs 7.59 +/- 1.735, P < 0.001), longer sleep duration (6.86 +/- 1.204 h vs 5.80 +/- 1.730 h, P < 0.001), and fewer awakenings (1.42 +/- 1.183 vs 2.04 +/- 1.835, P = 0.026) than group 2. CONCLUSION For hospitalized patients >= 50 years in age, the bowel preparation regimen comprising 2-L PEG + 30-mL lactulose + a low-residue diet produced a cleanse that was as effective as the 4-L PEG regimen and even provided better comfort.