This study aimed to assess the safety and efficacy of midazolam and ketamine as adjuvants to the peribulbar block in vitreoretinal surgeries. This randomized controlled trial included 93 adult patients undergoing vitreoretinal surgeries performed with peribulbar anaesthesia. Patients were randomly allocated to 3 groups (31 participants each): control (standard anaesthetic mixture), midazolam (standard mixture + midazolam), and ketamine (standard mixture + ketamine). The primary outcomes were onset of globe akinesia and duration of analgesia. Secondary outcomes were duration of motor blockade, onset of corneal anaesthesia and lid akinesia, and changes in vital data (blood pressure, oxygen saturation, and pulse rate). The ketamine group vs. the control and midazolam groups showed the most rapid onset of lid and globe akinesia (p < 0.001) and corneal anaesthesia (0.7 ± 0.2 vs. 1.5 ± 0.5 and 1.2 ± 0.4, respectively; p < 0.001) and the longest duration of both analgesia (3.7 ± 0.6 vs. 2.3 ± 0.4 and 3.1 ± 0.6, respectively; p < 0.001) and akinesia (3.8 ± 0.5 vs. 3.0 ± 0.4, and 3.7 ± 0.5, respectively; p < 0.001). The midazolam group showed better outcomes than controls, but the drug was less effective than ketamine. There were no significant differences in vital data among groups (p > 0.05). Ketamine is an effective adjuvant for peribulbar blockade. It enhances both motor and sensory blockade by hastening onset and prolonging duration. These effects are desirable in lengthier ophthalmic procedures such as vitreoretinal surgeries. The effects of ketamine were superior to those of midazolam.