AIM: To observe the efficacy and safety of pars plana vitrectomy (PPV) with eye position guided fluid-air exchange (FAX) and air tamponade in the treatment of rhegmatogenous retinal detachment (RRD). METHODS: RRD patients without severe proliferative vitreoretinopathy (PVR) C1 or more were enrolled. All patients underwent PPV combining with air tamponade. During operation, the primary retinal break(s) were placed at lower site and subretinal fluid was aspirated through the break(s) at the same time when eye position guided FAX was proceeding. Sufficient laser spots were made to seal the retinal break(s) after FAX, and filtered air was left in vitreous cavity as tamponade agent finally. The main outcomes were primary and final success rates, best corrected visual acuity (BCVA), and the secondary outcomes were rate of postoperative cataract surgery and high intraocular pressure. RESULTS: A total of 37 eyes (20 males and 17 females) with a follow-up time of ≥6mo were included. The range of RRD was 5.6±1.8h, and the number of retinal breaks was 1.9±1.2. The breaks located at inferior quadrants (between 3:00 and 9:00) in 5 cases (13.5%), and both superior and inferior breaks were found in 3 cases (8.1%). A total of 25 cases (67.6%) with macular detached involvement, 9 cases (24.3%) with intraocular lens, and 8 patients (21.6%) were treated with phacoemulsification and intraocular lens implantation together. The success rate of primary retinal reattachment was 100% (37/37). At 6mo postoperatively, BCVA (logMAR) was increased from 1.13±1.07 to 0.23±0.15 (P<0.001). Phacoemulsification combined with intraocular lens implantation was performed in 2 patients (5.4%), and one of them underwent macular epiretinal membrane peeling in addition (2.7%). Furthermore, high intraocular pressure was found in 4 cases (10.8%). CONCLUSION: PPV with air tamponade by eye position guided FAX can achieve a high reattachment success rate in the management of patients with RRD, and it has the advantages of short postoperative prone time and fewer operative complications.