Background Optimal observation periods and surgical predictive utility for iohexol in adhesive small bowel obstruction (ASBO) remain undefined. This study systematically evaluates iohexol's time-dependent therapeutic effects and its role in guiding surgical decisions.Methods We first conducted a meta-analysis of water-soluble contrast agents in ASBO. Subsequently, a retrospective cohort of ASBO patients (2020–2024) from Li Huili Hospital was analyzed. Iohexol recipients were 1:1 propensity score-matched with conventional management patients. Clinical outcomes (surgical rate, hospital stay, operative time) were compared. Time-dependent Cox regression analyzed iohexol's impact on symptom resolution across 0–24h, 24–48h, and > 48h post-admission, complemented by a 48-hour landmark analysis.Results The meta-analysis of twenty studies confirmed water-soluble contrast agents significantly reduce ASBO surgical rates and hospital stays. In our retrospective study, 103 iohexol patients were matched with 103 conventional treatment patients. The iohexol group showed a significantly lower surgery rate (16% vs. 28%, P = 0.043), a higher 48-hour resolution rate (79% vs. 61%, P = 0.01), and reduced hospital stay. Time-dependent Cox regression revealed iohexol's strong pro-resolution effect within 0–24h (HR = 2.92, P < 0.001), significantly attenuated at 24–48h (interaction HR = 0.42, P = 0.014), and non-significant beyond 48h. The 48-hour landmark analysis confirmed no significant benefit for patients unresolved by 48 hours.Conclusion Both analyses demonstrate iohexol enhances ASBO resolution and reduces hospital stay, with maximal benefit within the first 48 hours. Its efficacy is limited for patients unresolved after 48 hours. We recommend a systematic "48-hour iohexol assessment" approach to optimize treatment and prevent delayed surgery.