Purpose: To compare the vitreous loss complication rate of manual phacoemulsification cataract surgery with that of femtosecond laser-assisted cataract surgery., Setting: Mercy Eye Specialists, Springfield, Missouri, USA., Design: Retrospective single-center case series., Methods: Cataract surgeries from 2010 to 2014 performed by 4 surgeons were audited for rates of vitreous loss. Vitreous loss data were statistically analyzed with and without exclusions., Results: Of the total 7155 cases from 2010 to 2014, 3784 were consecutively performed using manual phacoemulsification from 2010 to 2012 and 3371 were performed using femtosecond laser-assisted cataract surgery from 2013 to 2014. The rate of vitreous loss with exclusions was 1.17% in the manual phacoemulsification group and versus 0.65% femtosecond laser-assisted group; without exclusions, the rate was 1.40% versus 0.77%. In absolute terms, the rate decreased for every surgeon in the study. The chi-square test showed a statistically significant association between the date of surgery, and thus technique, and vitrectomy cases (P < .05). Odds ratio analysis with exclusions versus without exclusions indicated that surgeries performed from 2010 to 2012 using manual phacoemulsification were 1.6 times and 1.8 times, respectively, more likely to have vitreous loss than surgeries performed from 2013 to 2014 using the femtosecond laser-assisted cataract surgery technique., Conclusions: Conversion from manual phacoemulsification to femtosecond laser-assisted cataract surgery resulted in a statistically significant decrease in vitreous loss. Because vitreous loss increases the risk for other serious complications of cataract surgery, this new finding has important implications for the safety of cataract surgery., Financial Disclosure: Proprietary or commercial disclosures are listed after the references., (Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)