BackgroundInadequate bowel preparation for colonoscopy remains an issue resulting in lower adenoma detection rates and increased cost. We assessed the efficacy, safety and tolerability of high-dose bowel preparations in subjects who previously had an inadequate colonoscopy preparation.MethodsWe performed a multi-step prospective trial of high-dose bowel preparations with subjects assigned to the dose higher than their previous inadequate preparation. Step 1: 1.5 times the standard-dose of polyethylene glycol 3350 (PEG, 459 g) and Gatorade; and Step 2: 2.0 times the standard-dose of PEG (612 g) and Gatorade, both were given as extended split-dose preparations. 69 outpatients consumed their preparation before a morning colonoscopy. The primary endpoint was colon cleanliness assessed by the Chicago bowel preparation scale (BPS). Safety was assessed by comparing a baseline basic metabolic panel (BMP) to a post-cleansing BMP. Patients with no history of inadequate colon cleansing who consumed standard doses of PEG (306 g to 357 g) and Gatorade were used as a comparison group. Tolerability of the bowel preparation was assessed using a subject-questionnaire.ResultsWhen compared to controls consuming standard-dose bowel preparations, subjects consuming high-dose preparations had no statistically significant difference in colon cleanliness as measured by the modified or total Chicago BPS scores or differences in tolerability. Baseline and post-cleaning BMPs were not significantly different other than the BUN falling (p< 0.0001) after the preparation.ConclusionsThe multi-step high-dose bowel cleansing protocol proved highly efficacious, safe and well tolerated in subjects who previously had an inadequate colonoscopy preparation.Trial registration: ClinicalTrials.gov NCT02661750.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12876-023-02663-0.