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Surgery is the treatment of choice for perforated peptic ulcer disease. The aim of the present review was to compare the perioperative outcomes of acute laparoscopic versus open repair for peptic ulcer disease.A systematic literature search was performed for randomized controlled trials (RCTs) published in PubMed, SCOPUS, and Web of Science.The search included eight RCTs: 615 patients comparing laparoscopic (307 patients) versus open peptic perforated ulcer repair (308 patients). Only few studies reported the Boey score, the Acute Physiologic Assessment and Chronic Health Evaluation score, and the Mannheim Peritonitis Index. In the RCTs, there is a significant heterogeneity about the gastric or duodenal location of peptic ulcer and perforation size. All trials were with high risk of bias. This meta-analysis reported a significant advantage of laparoscopic repair only for postoperative pain in first 24 hours (−2.08; 95% confidence interval, −2.79 to −1.37) and for postoperative wound infection (risk ratio, 0.39; 95% confidence interval, 0.23–0.66). An equivalence of the other clinical outcomes (postoperative mortality rate, overall reoperation rate, overall leaks of the suture repair, intra-abdominal abscess rate, operative time of postoperative hospital stay, nasogastric aspiration time, and time to return to oral diet) was reported.In this meta-analysis, there were no significant differences in most of the clinical outcomes between the two groups; there was less early postoperative pain and fewer wound infections after laparoscopic repair. The reported equivalence of clinical outcomes is an important finding. These results parallel the results of several other comparisons of open versus laparoscopic general surgery operations—equally efficacious with lower rates of wound infection and improvement in some measures of enhanced speed or comfort in recovery. Notably, the trials included have been published throughout a considerable time span during which several changes have occurred in most health care systems, not least a widespread use of laparoscopy and increase in the laparoscopic skills.Systematic review and meta-analysis, level III.