Purpose To evaluate the effect of hydrodissection on intraoperative performance during phacoemulsification of age-related nuclear cataracts. Setting Iladevi Cataract & IOL Research Centre, Ahmedabad, India, and Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. Methods In a prospective study, 86 eyes were randomly assigned to have multiquadrant hydrodissection (+HD, n = 48) or no hydrodissection (–HD, n = 38) during phacoemulsification of a grade 1 to 3 nuclear cataract. Excluded were patients with grade 4 or 5 nuclear sclerosis, a poorly dilating pupil, or associated ocular/systemic disease. Parameters assessed were nucleus and cortex removal time, the amount of fluid used for cortex removal, and the total amount of fluid used. The ease of nucleus rotation and cortical cleanup was also evaluated and graded subjectively as very easy, difficult, or very difficult. Data were analyzed using the Student t test and the chi-square test. Results The mean nucleus removal time was 355 seconds ± 237 (SD) and 474 ± 212 seconds in the +HD and –HD groups, respectively ( P = .09). The mean cortex removal time was significantly less in the +HD group than in the –HD group (79 ± 51 seconds and 220 ± 222 seconds, respectively) ( P = .007). Significantly less fluid (43%) was used for cortex removal in the +HD group than in the –HD group (mean 70 ± 45 mL and 123 ± 82 mL, respectively) ( P = .013), and significantly less total fluid (35%) was used in the +HD group (312 ± 132 mL and 422 ± 80 mL, respectively) ( P = .002). Nucleus rotation was easy in all eyes in the +HD group; 68.43% of eyes in the –HD group failed to achieve rotation ( P = .001). Cortex removal was very easy in 52.08% of eyes in the +HD group and easy in 47.90%; it was easy in 52.63% in the –HD group, difficult in 36.84%, and very difficult in 10.52%. Conclusion The use of multiquadrant cortical-cleaving hydrodissection made removal of the lens nucleus and cortex easier and faster during phacoemulsification of age-related nuclear cataracts.