Purpose: To evaluate the safety and efficacy of 25-gauge instrumentation for a variety of vitreoretinal conditions on previously nonvitrectomized eyes. Design: Single-center, retrospective, interventional case series. Participants: One-hundred forty eyes of 140 patients were evaluated at the Doheny Retina Institute from July 2002 to July 2003. Intervention: All patients underwent surgical procedures using the Millennium 25-gauge Transconjunctival Standard Vitrectomy system. Twenty eyes (14.3%) underwent procedures without vitrectomy. Main Outcome Measures: Postoperative visual acuity (VA), intraocular pressure, surgical time, postoperative inflammation, complications, and number of sutured sites. Results: No intraoperative complications were noted. No cases required conversion to 20-gauge machines. Ten cases (7.1%) involved single-site sclerotomy suture placement due to bleb formation at the conclusion of the procedure, but 5 of these entry sites were enlarged to facilitate larger instrumentation for tissue manipulation. Median VA improved from 20/250 (logarithm of the minimum angle of resolution, 1.08±0.47) preoperatively to 20/60 (0.47±0.30)-(P< 0.0001) at final visit. Mean follow-upwas 33.8±9.7weeks, and all eyes were observed for a minimum of 12 weeks. Mean total surgical time was 17.4±6.9minutes. Intraocular pressures remained stable throughout the postoperative course. Five eyes (3.8%) presented on day 1 with shallow choroidal detachments, but all resolved by day 7, and none required volume infusion during the postoperative period. All but one of these cases was within the first 50 procedures performed. No detectable inflammation was noted in any eyes by 4 weeks postoperatively. No case of retinal detachment or endophthalmitis was recorded. Conclusions: Transconjunctival surgery using 25-gauge instrumentation may hasten postoperative recovery by decreasing overall surgical time and postoperative inflammation. Procedures requiring minimal intraocular manipulation did not require sutures and, thus, may be better suited for this surgical modality. Purpose: To evaluate the safety and efficacy of 25-gauge instrumentation for a variety of vitreoretinal conditions on previously nonvitrectomized eyes. Design: Single-center, retrospective, interventional case series. Participants: One-hundred forty eyes of 140 patients were evaluated at the Doheny Retina Institute from July 2002 to July 2003. Intervention: All patients underwent surgical procedures using the Millennium 25-gauge Transconjunctival Standard Vitrectomy system. Twenty eyes (14.3%) underwent procedures without vitrectomy. Main Outcome Measures: Postoperative visual acuity (VA), No cases required conversion to 20-gauge machines. Ten cases (7.1%) involved single-site sclerotomy suture placement due to bleb formation at the conclusion of the procedure, but 5 of these entry sites were enlarged to facilitate larger inst Median VA improved from 20/250 (logarithm of the minimum angle of resolution, 1.08 ± 0.47) preoperatively to 20/60 (0.47 ± 0.30) - (P <0.0001) at final visit. Mean follow-up was 33.8 Mean total surgical time was 17.4 ± 6.9 minutes. Intraocular walls remained stable throughout the postoperative course. Five eyes (3.8%) presented on day 1 with shallow choroidal detachments, but all resolved by day 7, and none required volume infusion during the postoperative period. All but one of these cases was within the first 50 procedures performed. No detectable inflammation was noted in any eyes by 4 weeks postoperatively. No case of retinal detachment or Conclusions: Transconjunctival surgery using 25-gauge instrumentation may has postoperative recovery by decreasing overall surgical time and postoperative inflammation. Procedures require minimal intraocular manipu lation did not require sutures and, therefore, may be better suited for this surgical modality.