Purpose: To compare characteristics, clinical outcomes and complication profiles of a cohort of patients undergoing 27-gauge versus 23-gauge vitrectomy surgery at a tertiary medical center in the Middle East. Methods: This is a retrospective comparative study of indication-matched patients undergoing 27gauge versus 23-gauge pars plana vitrectomy for a set of predetermined diagnoses. Data including indications for surgery, clinical exams, visual outcomes, and complications were documented and analyzed. Results: A total of 22 patients who had 27-gauge pars plana vitrectomy were compared with 44 patients who had 23-gauge surgery for matched indications by a single retina surgeon. Mean follow-up was 14 months after surgery. Indications included macular pucker, macular hole, and vitreous hemorrhage. Both the rate of hypotony at postoperative day 1 and the need for sclerotomy stitching at the end of surgery were significantly more frequent in 23-gauge compared to 27-gauge cases (25% in 23-gauge compared to 0% in 27-gauge (p=0.012) and 18% in the 23-gauge compared to 0% in the 27-gauge (p=0.045), respectively). The mean duration of surgery was similar among groups (35 mins in the 27-gauge group versus 39 mins in the 23-gauge group (p=0.116)), and all eyes achieved anatomic success. In the 27gauge group, best-corrected visual acuity improved from a mean of 20/90 at baseline to a mean of 20/40 at 1 month (p=0.005) and in the 23-gauge group from a mean of 20/95 to 20/ 50 (p=0.001) with no statistical difference between the groups. Conclusion: In this cohort of patients undergoing vitrectomy at a tertiary eye center, the rate of hypotony and the need for sclerotomy suturing were significantly less in the 27-gauge group versus the 23-gauge group. Surgical outcomes were similar in both study groups. The use of the novel 27-gauge instrument system is useful in selected vitreoretinal diseases and appears comparable to the widely used 23-gauge system.