Background: Adequate bowel cleansing is critical for effective screening colonoscopy. While numerous risk factors influence preparation adequacy, residual risks warrant investigation in cohorts with high baseline preparation quality. This study aimed to identify residual risk factors for inadequate bowel preparation in a large real-world cohort with high adequacy rates.

Methods: This retrospective analysis included 15,669 patients scheduled for colonoscopy using 3L/2L polyethylene glycol (PEG) or sodium picosulfate regimens between November 2022 and November 2023. Statistical analyses assessed comorbidities (diabetes, constipation, Parkinson’s disease, gastrointestinal surgery history), preparation-related factors (regimen type, low-residue diet, dimethicone use), and adverse reactions (bloating, vomiting). Multivariable logistic regression and subgroup analyses identified risk factors for inadequate preparation and assessed intractability.

Results: Among 15,193 colonoscopies analyzed, multivariable regression identified independent protective factors: 3L-PEG split regimen, female sex, hospitalization, low-residue diet, dimethicone use, completion of preparation, and absence of abdominal pain/bloating. Independent risk factors included age ≥57 years, gastrointestinal surgery history, diabetes, constipation, tricyclic antidepressant use, and spinal injury. Subgroup analysis confirmed gastrointestinal surgery history as a consistent risk factor across all subgroups (age, gender, hospitalization, BMI; OR >1, p<0.05; interaction p>0.05). However, the 3L-PEG regimen eliminated this risk (OR 1.27, 95% CI 0.60–2.69, p=0.52). Diabetes remained a significant risk factor across all subgroups (all ages, genders, inpatient/outpatient settings, BMI categories, and preparation regimens; OR>1, p<0.05; interaction p>0.05), persisting even under the 3L-PEG regimen’s protective effect (OR 2.80, 95% CI 1.74–4.50, p<0.01).

Conclusion: In a cohort with high bowel preparation adequacy rates, age ≥57 years, gastrointestinal surgery history, diabetes, constipation, tricyclic antidepressant use, and spinal injury represent residual independent risks. The 3L-PEG split regimen eliminates the risk associated with gastrointestinal surgery history, but diabetes persists as an intractable risk factor. Future efforts should prioritize developing diabetes-targeted bowel preparation strategies to improve adequacy in high-risk populations.