Aim: To study outcomes after using perfluoro-n-octane (PFO) as a short-term postoperative vitreous substitute in eyes undergoing primary vitrectomy with or without sclera buckling for complex rhegmatogenous retinal detachments with inferior/multiple breaks or giant retinal tears (GRTs) or retinal detachment with extensive proliferative vitreoretinopathy (PVR). Methods: A prospective study was carried out where in 43 patients (Group 1) PFO was exchanged with silicon oil in the same surgical procedure and in 22 patients (Group 2) PFO was kept for 3 days and then exchanged with silicon oil by a separate surgical procedure. The respective surgeon took the decision whether to exchange PFO on the same day or after 3 days. The patients were followed up for 6 months to analyze the anatomical attachment rates, visual acuity gain, and postoperative complications in both the groups. Results: There were 33 male and 10 female patients in group 1 and 18 male and 4 female patients in group 2. Mean age distribution in group 1 was 38.88 years (SD±21.45) and in group 2 was 38.09 years (SD±16.36).