Background:Dexamethasone or dexmedetomidine may improve the quality of peribulbar block.Aim:The aim of this study is to compare the effects of adding either dexamethasone or dexmedetomidine to peribulbar block on the efficacy, intraocular pressure (IOP), time to first analgesic request, total analgesic requirement, and side effects in patients undergoing vitreoretinal surgery.Design:This was a clinical prospective randomized study.Patients and Methods:One hundred and fifty adult patients scheduled for vitreoretinal surgery with peribulbar block were randomized into three groups (50 patients each). Group I received 3.5 ml of 0.5% bupivacaine and 3.5 ml of 2% lidocaine + 1 ml normal Saline. 4 mg dexamethasone and 25 μg dexmedetomidine in 1 ml were added to the local anesthetic mixture in Groups II and III respectively. Onset and duration of sensory and motor blocks, adequate time to start surgery, IOP, time to first request of rescue analgesia, total analgesic consumption, and side effects were recorded. The statistical software SPSS 16 was utilized for statistical analysis.Results:Dexamethasone and dexmedetomidine groups showed significantly prolonged duration of corneal anesthesia (234.07 ± 1.37 and 233.54.1.97 min respectively), prolonged lid and globe akinesia (194.27 ± 1.63 and 194.73 ± 2.35 min respectively) with prolonged time to first request of analgesia and less consumption of rescue analgesia as compared to control group (P < 0.05) with non significant differences between both groups (P > 0.05). The onset of corneal anesthesia as well as lid and globe akinesia were enhanced in dexmedetomidine group compared to the other two groups (P < 0.05). In addition, the measurement of IOP was significantly less in the dexmedetomidine group after 10 min. All the patients were hemodynamically stable with no side effects observed.Conclusion:The addition of dexamethasone and dexmedetomidine to local anesthetic mixture in peribulbar block for vitreoretinal surgeries provided safe and effective block with prolonged duration and decreased requirements of postoperative analgesia with better quality for dexmedetomidine group regarding the fast onset of the block and reduced IOP.