Background <p>Surgical site infections (SSIs) remain a major concern after abdominal surgery, with incidences of 15–22%. Intraoperative wound irrigation (IOWI) before closure is routinely performed to reduce bacterial contamination, but the benefit of antiseptic irrigation, such as aqueous chlorhexidine, remains uncertain.</p> Methods <p>This double-blind, randomized controlled trial was conducted at the Faculty of Medicine, Vajira Hospital, Bangkok, Thailand. A total of 408 adults undergoing abdominal surgery with clean-contaminated and contaminated wounds were randomized (1:1) to receive IOWI with either aqueous chlorhexidine or normal saline before skin closure. Randomization was computer-generated with block design, and outcomes were assessed at 30&#xa0;days postoperatively.</p> Results <p>Among 408 patients (204 per group), SSIs occurred in 21 patients (10.3%) in the aqueous chlorhexidine group and 28 (13.7%) in the saline group (overall 12.0%). The difference was not statistically significant (risk difference − 3.4%; 95% CI − 9.7–2.9%; <i>P</i> = 0.27). No significant differences were found in wound seroma, evisceration, hospital stay, or pain scores.</p> Conclusions <p>Aqueous chlorhexidine irrigation did not demonstrate statistically significant superiority over normal saline for preventing SSI in this population. As this trial was neither designed nor powered as an equivalence or non-inferiority study, the absence of a statistically significant difference should not be interpreted as evidence of equivalence between the two irrigation strategies.</p> Trial registration <p>Thai Clinical Trials Registry Number (TCTR20211027010).</p>