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BACKGROUND & AIMS The Potential benefits and possible risks of perioperative supplementation with probiotics/synbiotics in surgical patients are not fully understood. Recent evidence has rapidly evolved and conveys conflicting results. Thus, we undertook a meta-analysis of randomized controlled trials (RCTs) to valuate the effectiveness, safety, cost-effectiveness and quality of life of perioperative supplementation with pro-/synbiotics. METHODS We systematically searched PubMed, Embase and the Cochrane Library through October 2015 to identify RCTs that assessed the effects of perioperative supplementation with pro-/synbiotics in surgical patients. The predefined primary efficacy outcome was surgical site infection (SSI). Random-effects model was applied to pool outcome data accounting for clinical heterogeneity. RESULTS Our meta-analysis included data from 34 trials comprising 2634 participants, of whom 1300 received perioperative pro-/synbiotics intervention and 1334 received valid control treatment. Compared with the control group, patients in the pro-/synbiotics group had a lower risk of SSI (relative risk: 0.65; 95% confidence interval: 0.51, 0.84; P = 0.0007). Trial sequential analysis confirmed the evidence was sufficient and conclusive. Subgroup analyses indicated the findings were consistent in all subgroup analyses except for the probiotics, enteral feeding, pre-/postoperative and live transplantation subgroups. Pro-/synbiotics also reduced the incidence of other infectious complications (including any infection, pneumonia, urinary tract infection, wound infection and sepsis); shortened antibiotic therapy, intensive care unit stay and hospital stay; and promoted earlier first defecation and first bowel movement. Pro-/synbiotics further reduced the incidence of abdominal side effects, lowered hospital costs and improved the Gastro-Intestinal Quality of Life. CONCLUSIONS For surgical patients, perioperative supplementation with pro-/synbiotics is effective in preventing or controlling SSI and other infectious complications. Perioperative pro-/synbiotics might also be associated with fewer side effects, lower hospital cost and better quality of life. Current evidence indicated that perioperative synbiotics supplementation is preferred and recommended as an adjunct in surgical patients.