Objective: To evaluate a novel pars plana vitrectomy (PPV) approach with aqueous tamponade for repair of primary pseudophakic rhegmatogenous retinal detachment (RRD). Design: Prospective, noncomparative, interventional case series. Participants: Sixty nonconsecutive patients (60 eyes) with primary pseudophakic RRD. Intervention: Patients underwent PPV alone with injection of perfluoro-n-octane followed by fluid-air exchange and transscleral diode laser retinopexy and then balanced salt solution (BSS) tamponade. All patients were observed for at least 1 year. Main Outcome Measures: Anatomic outcome, visual acuity (VA), and complications. Results: The mean follow-up period was 16.4 months (range, 12.1-21.5). Preoperatively, 32 patients (53.3%) had 1 break and 28 patients (46.7%) had 2 to 4 breaks (mean, 2.7). Intraoperatively, 108 retinal breaks were identified, 82 (75.9%) superior and 26 (24%) inferior. Eight breaks in 8 patients that were not seen preoperatively or intraoperatively were diagnosed after air-BSS exchange. Mean preoperative best-corrected VA (BCVA) was 20/700 (range, hand movements [HM]-20/20). Final BCVA was a mean of 20/59 (range, 20/200-20/20). For the 13 eyes with macula-attached RRD, BCVA was the same preoperatively and postoperatively (mean, 20/27; range, 20/50-20/20). For the 47 eyes with macula-detached RRD, the mean BCVA was 20/888 preoperatively (range, HM-20/50) and 20/68 postoperatively (range, 20/200-20/20). Final VA was ≥20/40 in 34 of 60 eyes (56.6%). Primary retinal reattachment (attachment at 1 month postoperatively) was attained in 59 of the 60 patients (98.3%). The single failure was due to a new break postoperatively; this break was treated by pneumatic retinopexy and photocoagulation of the break. At the 12-month follow-up visit, reattachment had been attained in all 60 eyes (100%). Postoperatively, 1 patient (1.6%) had hypotony at the 1-day postoperative visit, but intraocular pressure was 14 mm at the 4-day visit, and 2 patients (3.3%) had mild vitreous hemorrhage during the first 48 hours that resolved spontaneously during the following 10 days. Conclusion: Pars plana vitrectomy with laser retinopexy followed by BSS tamponade is effective for intraoperative sealing of retinal breaks causing pseudophakic RRD. We did not identify safety concerns in this 60-patient series. © 2007 American Academy of Ophthalmology.