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Introduction: The potential benefit of intraoperative wound irrigation (IOWI) in preventing surgical site infection (SSI) remains unclear. The use of antimicrobial agents (AMA) or antiseptic agents (ASA) is controversial worldwide. Methods: We performed a systematic review and meta‐analysis of randomized clinical trials comparing AMA or ASA with saline solution in patients who underwent abdominal surgery. Sub‐analyses were performed on the type of surgery, type of intervention agent, and wound classification. Results: Nineteen studies comprising 4915 patients undergoing abdominal surgery were included. SSI was observed in 207 out of 2504 patients in the intervention group (8.26 %) and 344 out of 2411 patients in the control group (14.27%). Overall, intraoperative wound irrigation (IOWI) with AMA or ASA was associated with a lower SSI (Odds ratio (OR) 0.62; 95% CI 0.47, 0.82; p < 0.01; I2 = 50%). Sub‐analyses have shown a tendency for decreased SSI in patients from emergency surgery (OR 0.46; 95% CI 0.30, 0.70; p < 0.01; I2 = 23%), patients with contaminated wound (OR 0.48; 95% CI 0.31, 0.74; p < 0.01; I2 = 24%), and either the use of AMA or ASA (OR 0.53 vs. 0.65). Conclusion: The overall use of AMA or ASA before skin closure was associated with decreased SSI. Lower rates of SSI were observed in the subgroup analysis. Furthermore, we must consider the critical heterogeneity of the studies. [ABSTRACT FROM AUTHOR]