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To determine the efficacy and complications of pars plana vitrectomy (PPV) and adjunct surgeries for aqueous misdirection refractory to medical therapy.A retrospective review of consecutive eyes with refractory aqueous misdirection at the King Khaled Eye Specialist Hospital between 2002 and 2010. Patients underwent two-port and three-port pars plana vitrectomy (PPV) with adjunct procedures including pars plana lensectomy combined with posterior capsulectomy, hyaloido-zonulo-iridectomy, and synechiolysis. Main outcome measures included anatomical success, functional success, and factors associated with the outcomes.Sixty-nine eyes were evaluated over a mean follow-up period of 17.6 ± 3.8 months (3–156 months). Anatomical success was achieved in 62 eyes (90%) and functional success in 54 eyes (78%) that underwent PPV as a primary surgery. The factors associated with the altering misdirected aqueous flow and reducing intraocular pressure significantly associated with a two-line improvement of best-corrected visual acuity included surgical treatment within 4 weeks of presentation (P = 0.004) and preoperative intraocular pressure (P = 0.001). The success of two-port PPV and standard three-port PPV was similar (P = 0.7). The intraoperative and postoperative complications included retinal detachment in two eyes and endophthalmitis in one eye.The PPV was effective for managing aqueous misdirection refractory to medical therapy. Two-port or three-port PPV did not change the success rate but early surgery improved both anatomical and functional outcomes.