Background <p>Bowel preparation quality is critical for effective colonoscopy. We aimed to evaluate seasonal variation in bowel preparation adequacy and to determine whether season modifies the association between preparation regimen and inadequate bowel preparation.</p> Methods <p>This single-center retrospective study included 853 patients undergoing health-screening colonoscopy in 2024 who received either a split-dose regimen (SPD, n = 388) or same-day dosing (SDD, n = 465) of polyethylene glycol–based preparation. Multivariable logistic regression was used, with effect modification tested via a Season × Regimen interaction term (likelihood ratio test [LRT], df = 3). Bootstrap resampling (5,000 replicates) and parametric-bootstrap empirical power analyses were performed to evaluate interaction robustness.</p> Results <p>Inadequate preparation was most frequent in winter (20.9%) and least frequent in autumn (9.8%). Without the interaction term, winter was associated with higher odds of inadequate preparation versus spring (odds ratio [OR] = 2.17, 95% confidence interval [CI] 1.23–3.90). A significant Season × Regimen interaction was observed (P = 0.047). In winter, SDD versus SPD was associated with lower odds of inadequate preparation (adjusted OR = 0.43, 95% CI 0.21—0.87), whereas no significant association was seen in other seasons. Higher body weight, anxiety, and constipation were independently associated with inadequate preparation. Bootstrap re-estimation showed wide CIs for interaction terms (e.g., winter × SDD OR = 0.25, 95% CI 0.07–0.86), and empirical power for detecting the interaction was 0.65.</p> Conclusions <p>This study identified seasonal variation in bowel preparation quality and a potential season-by-regimen interaction. In winter, SDD was associated with lower odds of inadequate preparation compared with SPD; however, this finding requires confirmation in larger prospective studies.</p>