Objective: We compared the routine use of perioperative selective decontamination of the digestive tract (SDD) for elective gastrointestinal surgery with placebo in a randomized controlled trial. Alongside this trial, a cost-effectiveness analysis from a provider perspective was performed. Methods and Results: A total of 289 patients undergoing elective surgery of the digestive tract were randomized to either SDD (143 patients) or placebo (146 patients). Routine use of SDD led to less patients with an infectious complication compared with placebo (p = 0.028). Mean total costs per patient were slightly less (EUR 2,604; 95% CI –6,292 to 1,084) in patients randomized to SDD (EUR 12,031) compared to patients randomized to placebo (EUR 14,635). Costs of hospitalization were the main determinant of the cost difference between the groups. The incremental cost-effectiveness ratio per prevented occurrence of ≥1 infectious complications per patient was –EUR 23,164, indicating the superiority of SDD over placebo. Conclusion: This study shows that in patients undergoing elective gastrointestinal surgery, the routine use of SDD is less expensive and economically more efficient than placebo in reducing the number of patients with infectious complications.

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