OBJECTIVE To evaluate the efficacy and safety of hyaluronidase as an adjuvant to mepivacaine for retrobulbar anesthesia in cataract surgery. METHODS Department of Ophthalmology, Ludwig-Maximilians-University, Munich, and Eye Center Munich East, Munich-Haar, Germany. METHODS Eyes having cataract surgery at 1 of the 2 centers were included in this prospective randomized double-blind placebo-controlled clinical trial. Retrobulbar anesthesia was administered by the surgeon using a solution of 5 mL mepivacaine 1% with additional hyaluronidase (Hylase Dessau) 75 IU (40 eyes) or additional placebo (40 eyes). The main target parameter was akinesia 5 minutes after administration of the study medication. Secondary parameters were akinesia at later times, additional injections, ptosis of the upper eyelid, time to reach complete anesthesia, assessment of pain using a visual analog scale, assessment of efficacy and tolerability by the patient and the surgeon, and adverse events. RESULTS Complete akinesia 5 minutes after retrobulbar injection was reached in significantly more cases in the hyaluronidase group (29) than in the placebo group (13) (P < .001). Additional injections were necessary in 5 placebo-treated eyes. The administration of hyaluronidase yielded significantly better results than the placebo in terms of ptosis, time to reach complete anesthesia, assessment of efficacy, tolerability, and postoperative pain. No adverse events occurred in either group. CONCLUSIONS The addition of hyaluronidase to mepivacaine for retrobulbar anesthesia in cataract surgery enhanced the safety of the surgical procedure due to more complete akinesia and quicker onset of complete anesthesia.