Purpose: To compare the efficacy of a single application of lidocaine 2% gel with tetracaine 0.5% drops for topical anesthesia in dear corneal cataract surgery. Setting: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Methods: A preliminary toxicity study applied lidocaine 2% gel in the conjunctival fornices of rabbit eyes (n = 9). Biomicroscopic examination was performed and then enucleation at sequential intervals after the application. Intentional intracameral injection of lidocaine gel was performed (n = 3), followed by enucleation. Histopathological analysis was performed on all eyes. A randomized clinical trial comparing topical anesthesia in clear corneal cataract surgery was performed in 25 eyes of 25 patients (12 eyes randomly assigned to lidocaine gel, 13 eyes to tetracaine drops). Corneal sensation was measured with the Cochet-Bonnet aesthesiometer before application of the topical anesthesia, 5 minutes after application, and at the conclusion of surgery. Additional intraoperative local anesthesia and systemic sedation were recorded. Patients' subjective level of comfort was reported 20 minutes after surgery, and the surgeon's perception of patients' comfort was also noted. Results: In rabbits, lidocaine gel did not cause clinical or histopathological alteration of the ocular tissues. In the clinical study, median corneal sensitivity before application, after 5 minutes, and postoperatively was 6, 0, 0 (maximum sensitivity = 6), respectively, in the lidocaine gel group and 5, 0, 0, respectively, in the tetracaine drops group. Additional local anesthesia was administered in 17% and 31% of patients, respectively. Satisfactory com- fort was reported by 58% in the lidocaine gel group and 62% in the tetracaine drops group. Conclusions: A single application of lidocaine 2% gel was a safe and effective alternative to multiple topical anesthetic drops for clear corneal cataract surgery. Lidocaine 2% gel was similar to tetracaine drops in provision of corneal anesthesia and patient comfort, while causing no significant toxicity to the ocular surface.