Background <p>Postoperative delirium (POD) is one of the most prevalent complications in elderly surgical patients. This study aimed to assess whether the use of transversus abdominis plane block (TAPB) is associated with a reduced incidence of POD in this patient population.</p> Methods <p>In this retrospective cohort study (January 2016 to March 2022), we analyzed elderly patients (≥ 65 years) who underwent major gastrointestinal surgery. The association between TAPB and POD was evaluated using multivariate logistic regression, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and subgroup analyses.</p> Results <p>Among 5,220 patients, the incidence of POD was significantly lower in patients receiving TAPB. This protective effect was consistently demonstrated in Multivariate regression analysis, OR was 0.351 (95% CI 0.163 to 0.663, <i>P</i> = 0.003). Consistent findings emerged after PSM (<i>P</i> = 0.007) and IPTW (<i>P</i> &lt; 0.001) adjustment. TAPB was also associated with significantly reduced sufentanil requirements (<i>P</i> &lt; 0.001) and shorter hospital length of stay (<i>P</i> &lt; 0.001). However, 30-day postoperative mortality did not differ significantly between groups. Subgroup analyses stratified by age, sex, albumin, surgical site, Body mass index (BMI), and dexmedetomidine demonstrated no significant interaction effects across all variables (<i>P</i>-interaction &gt; 0.05).</p> Conclusions <p>Current evidence suggests that the use of TAPB is significantly associated with a reduced incidence of POD in elderly patients undergoing major gastrointestinal surgery.</p> Trial registration <p>The trial was registered on ClinicalTrials.gov on February 14, 2025, with the identifier NCT06829108</p>