Although usually safe, retrobulbar anesthesia and peribulbar anesthesia have potentially sight- and life-threatening complications. Although it has been suggested that peribulbar anesthesia is as effective and safer than retrobulbar anesthesia, no large study has addressed the true rate of complications. To determine the efficacy and safety of peribulbar anesthesia, this study prospectively examined 16,224 consecutive peribulbar blocks. Twelve centers in the United States, Germany, and Chile participated in the study. After a peribulbar block was administered, the degree of akinesia, amaurosis, percentage of supplemental blocks required, and side effects and complications occurring after the block and for six weeks were recorded. Perioperative and late optic nerve complications were included. To approximate a real-life situation, ophthalmologists, anesthesiologists, and certified registered nurse anesthetists performed the blocks. Ninety-five percent of patients achieved a 95% or greater degree of akinesia. The incidence of complications in the consecutive cases was low. Orbital hemorrhage occurred in 12 cases (0.74%). There was one globe perforation (0.006%), two expulsive hemorrhages (0.013%), one grand mal seizure (0.006%), and no cases of cardiac or respiratory depression or deaths. Peribulbar is as effective as retrobulbar anesthesia and appears to lead to fewer sight- and life-threatening complications, even when slightly different peribulbar techniques are used. This is especially true when the anesthetic is administered with a 1 1/4-inch or shorter needle with the eye in the primary position, followed by ten to 15 minutes of ocular compression.