In this prospective, interventional study the authors evaluated the risk factors for elevated intraocular pressure (IOP) after pars plana vitrectomy (PPV) with silicone oil injection (SOI). This study included 254 eyes of 254 patients, with a mean age of 55.33 (±16.29) years and a male-to-female ratio of 2:1. The mean preoperative IOP was 12.5±5.00mmHg. Indications for surgery were primary uncomplicated RRD (110 eyes; 43.3%), recurrent uncomplicated rhegmetogenous retinal detachment (RRD) (19 eyes; 7.5%), primary RRD with proliferative vitreoretinopathy (PVR) (25 eyes; 9.8%), recurrent RRD with PVR (30 eyes; 11.8%), proliferative diabetic retinopathy (PDR) with TD (41 eyes; 16.1%), traumatic RRD (14 eyes; 5.5%), and macular hole (MH) (15 eyes; 5.9%). 1,000-cSt and 5,000-cSt SO viscosity was used in simple and complicated cases, respectively. Mean duration of SO tamponade was 8.79±8.73 months (median six months). Follow-up visits were at day one, weeks one and two, months one, two, three and six and then every six months. The last follow-up visit was at the point of SO removal. The onset of IOP elevation was classified into three groups: early (≤1 week), intermediate (>1–6 weeks), and late (>6 weeks up to the time of SO removal). One hundred and twenty-two eyes (48%) developed ocular hypertension (>21mmHg), 61.5% (75 eyes) of which occurred in the early postoperative period, 28.7% (35 eyes) in the intermediate period (one to six weeks), and 9.8% (12 eyes) in the late period (>6 weeks). Of these cases, 39, 18 and seven eyes, respectively, had an IOP ≥25mmHg, while the remaining cases ranged between 21 and 25mmHg. Most cases responded to topical treatment, but 16 eyes (6.3%) needed surgery. In the postoperative follow-up period, 18 eyes (7.1%) had SO in the anterior chamber (AC). Preoperative IOP, high myopia, and previous cataract surgery all conferred a higher risk for increased IOP, whereas diabetes conferred a reduced risk for increased IOP. Patients that developed elevated IOP had a statistically significant higher preoperative IOP (13.48 vs. 11.46mmHg; p=0.001) and tended to be younger (53.3 vs. 57.2 years; p=0.06). Furthermore, patients who had a late increase in IOP had higher preoperative IOP values than those with an early-onset IOP increase (17.92 vs. 12.6mmHg; p=0.01). The risk factors for IOP elevation following SO tamponade were, preoperative IOP (relative risk 1.12), pseudophakia (relative risk 1.93), and 1000-cSt SO (1.63), while diabetes mellitus (relative risk 0.43) and intraoperative membrane segmentation and delamination were found to be protective factors against IOP elevation. IOP should be monitored regularly and for a long period in all patients undergoing PPV and SO tamponade. Risk factors for ocular hypertension development are pseudophakia, high myopia, high preoperative IOP, and low-viscosity SO to pseudophakic patients and patients that received low viscosity SO.