Introduction. Laparoscopic repair of perforated peptic ulcer (PPU) remains controversial mainly due to its safety and applicability in critically ill patients. &e aim of this study is to compare the outcomes of laparoscopy versus laparotomy in the treatment of PPU. Methods. Single-institutional, retrospective study of all patients submitted to surgical repair of PPU between 2012 and 2019. Results. During the study period, 169 patients underwent emergent surgery for PPU. A laparoscopic approach was tried in 60 patients and completely performed in 49 of them (conversion rate 18.3%). &e open group was composed of 120 patients (included 11 conversions). Comparing the laparoscopic with the open group, there were significant differences in gender (male/female ratio 7.2/1 versus 2.2/1, respectively; p = 0.009) and in the presence of sepsis criteria (12.2% versus 38.3%, respectively; p = 0.001), while the Boey score showed no differences between the two groups. &e operative time was longer in the laparoscopic group (median 100' versus 80', p = 0.01). Laparoscopy was associated with few early postoperative complications (18.4% versus 41.7%, p = 0.004), mortality (2.0% versus 14.2%; p = 0.02), shorter hospital stay (median 6 versus 7 days, p = 0.001), and earlier oral intake (median 3 versus 4 days, p = 0.021). Conclusion. Laparoscopic repair of PPU may be considered the procedure of choice in patients without sepsis criteria if expertise and resources are available. &is kind of approach is associated with a shorter length of hospital stay and earlier oral intake. In patients with sepsis criteria, more data are required to access the safety of laparoscopy in the treatment of PPU. [ABSTRACT FROM AUTHOR]