To compare outcomes of 25-gauge pars plana vitrectomy (PPV) and sulfur hexafluoride (SF6) gas for primary rhegmatogenous retinal detachment (RRD) associated with multiple-quadrant versus single-quadrant breaks. A retrospective study of patients with RRD who underwent 25-gauge PPV with breaks involving multiple quadrants (Group A) or versus a single quadrant (Group B). One hundred eighteen eyes of 118 patients with a mean age of 60.4 years ± 11.8 years were reviewed, 27 with multiple-quadrant breaks and 91 with single-quadrant breaks. Single surgery anatomical success was achieved in 92.6% of Group A versus 93.4% of Group B patients (P = .88). The location and number of quadrants did not account for the variation in single surgery success or visual outcome. RRD with multiple-quadrant breaks is not associated with worst outcomes than single-quadrant breaks when treated with 25-gauge PPV and SF6 gas. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:820-827.].