Purpose: To compare anatomical and functional outcomes of 25-gauge transconjunctival sutureless pars plana vitrectomy (PPV) to standard 20-gauge 3-port PPV for the treatment of pseudophakic rhegmatogenous retinal detachments with inferior breaks. Methods: Retrospective review of 78 consecutive eyes from 78 patients undergoing primary vitrectomy with a minimum of 3-month follow-up. Thirty patients underwent 25-gauge PPV and 48 patients underwent 20-gauge PPV from May 1993 to July 2008. Variables and outcome measures included patient demographics, retinal reattachment, best-corrected visual acuity, macular status, postoperative intraocular pressures, and surgical complications. Results: Preoperative characteristics were similar in both groups. Single operation success rate was 25/30 (83.3%) for 25-gauge cases and 43/48 (89.6%) for 20-gauge cases (P = 0.50). Transient hypotony occurred in 6/30 25-gauge eyes and 1/48 20-gauge eyes (P = 0.01), whereas hypertension occurred in 10/30 25-gauge cases and 15/48 20-gauge cases. All but 2 eyes were attached at final follow-up (97%). At final follow-up, mean best-corrected visual acuity was 0.28 and 0.32 for the 25-gauge and 20-gauge groups (P = 0.74). Conclusion: Outcomes of 20-gauge versus 25-gauge PPV for the management of pseudophakic inferior rhegmatogenous retinal detachments were not significantly different, with hypotony being the most significant postoperative complication in the 25-gauge group as compared with the 20-gauge group.