To evaluate the effect of a high-vacuum setting versus a low-vacuum setting on the efficiency of phacoemulsification. Sunderland Eye Infirmary, Sunderland, United Kingdom. Prospective clinical trial. Consecutive patients having cataract surgery in 2014were recruited. Cataract surgery was performed by 2 experiencedsurgeons using a phacoemulsification machine with monitored forced infusion. The cataractous lens was split into 2 heminuclei using the stop-and-chop technique; in 1 heminucleus, phacoemulsification and aspiration used a high-vacuum setting (600mm Hg; treatment group) and in the other heminucleus, a low-vacuum setting (350mm Hg; control group). The high and low settings were alternated by case per the operating list to reduce surgeon bias. The main outcome measures were cumulative dissipated energy (CDE) and active heminucleus removal time. One hundred sixty patients (160 eyes) were enrolled in the study, and 158 were included in the analysis. The CDE per heminucleuswas significantly lower with the high-vacuum setting than with the low-vacuum setting (mean 2.81 percent-seconds; 95% confidence interval (CI), 2.44-3.21 versus 3.81 percent-seconds; 95% CI, 3.38-4.20; P<.001). The active heminucleus removal time was significantly shorter in the high-vacuum group than the low-vacuum group (mean 27.77seconds; 95% CI, 25.26-30.19 versus 33.59seconds; 95% CI, 31.07-35.92; P<.001). The observed differences were independent of the surgeon, patient age and sex, incision size, and nucleus density. No intraoperative complications were observed in either group. A high-vacuum setting improved phacoemulsification efficiency using an active fluidics system and torsional phacoemulsification.