To report the initial experience and safety profile of 23-gauge pars plana vitrectomy (PPV) in eyes undergoing vitreoretinal surgery. Retrospective, multicenter, consecutive, interventional case series. The inclusion criteria for this study included eyes that underwent primary, 23-gauge PPV for various indications including, but not limited to, epiretinal membrane, nonclearing vitreous hemorrhage, idiopathic macular hole, and rhegmatogenous retinal detachment (RD), and postoperative follow-up of at least 12 weeks. Exclusion criteria included history of prior vitrectomy, glaucoma filtration surgery, or administration of gas at expansile concentrations. Main outcome measures included best-corrected Snellen visual acuity (VA), intraocular pressure (IOP), intraoperative complications, and postoperative complications. Ninety-two patients met the inclusion criteria. The overall VA improved from 20/238 (range, 20/25 to hand motions [HM]) preoperatively to 20/82 (range, 20/20 to HM) postoperatively (P < .001). Each surgical indication experienced a statistically significant VA improvement. Intraoperative complications included retinal tears observed in two eyes (2.2%). Sclerotomy sutures were required intraoperatively in two eyes (2.2%). Postoperative complications included postoperative day 1 hypotony in six eyes (6.5%), a retinal tear in one eye (1.1%), and a recurrent RD in one eye (1.1%). No cases of endophthalmitis were observed. Intraoperative and postoperative complications were rare in this series of 23-gauge vitrectomy. Postoperative day 1 hypotony was the most common complication observed. All cases of postoperative hypotony resolved at postoperative week 1 without intervention. Retinal tear or detachment was an uncommon complication in the intraoperative and postoperative settings. Postoperative endophthalmitis was not noted in this case series.