Purpose To evaluate the efficacy of retro-peribulbar and subconjunctival anesthesia associated with intravenous sedation in patients undergoing evisceration and orbital implant placement. Methods The charts of 217 patients who underwent evisceration with trans-scleral implant placement were reviewed. Midazolam and fentanyl were used for intravenous sedation. For local anesthesia, a combination of lidocaine with epinephrine and bupivacaine was injected into the retrobulbar, upper peribulbar, and subconjunctival areas. The intraoperative pain and need for supplemental anesthetic injection were recorded prospectively. Results The surgery was performed with local anesthesia in 116 patients (53%) and with general anesthesia in 101 patients (47%). Patients were significantly older in the local anesthesia group than in the general anesthesia group (mean age, 59.9 years vs 45.2 years; P < .05). Supplemental retrobulbar anesthesia was required in 5 patients (4.3%). Transition to general anesthesia was required in 1 patient (0.9%) due to severe anxiety. Orbital hemorrhage developed after retrobulbar injection in 1 patient (0.9%), but did not preclude performing evisceration. Conclusions Combined retro-peribulbar and subconjunctival anesthesia with intravenous sedation can provide safe and effective intraoperative analgesia for evisceration surgery with trans-scleral implant placement.