The study aims to compare the efficacy/safety of femtosecond laser-assisted cataract surgery (FLACS) vs. conventional phacoemulsification cataract surgery (CPCS). A systematic search/analysis of PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov up to January 2023 was conducted without date/language restrictions. Weighted mean differences, risk ratios, and Hedges' g with 95% confidence intervals were calculated. The stability of results was assessed using trial sequential analysis (TSA). International Prospective Register of Systematic Reviews Registration No. PROSPERO CRD42023393323. Forty-six randomized controlled trials (8,871 eyes) revealed that FLACS yielded a significantly better corrected distance visual acuity (CDVA) 1 week postoperatively (P = 0.011) with no significant differences in CDVA beyond 1 week (P = 0.161, 0.429, 0.403), or in uncorrected distance visual acuity (P = 0.171, 0.136, 0.322, 0.149), spherical equivalent, or surgically induced astigmatism. Concerning safety outcomes, no significant differences were observed in overall complications (P = 0.999). These findings were supported by TSA. Ultimately, the overall complications, patient-reported health, visual, and daily-activity outcomes were not significantly different between FLACS and CPCS. Regarding extended-term and patient-centered outcomes, we identified no substantial disparities in visual acuity, complications, or patient-reported outcomes between FLACS and CPCS. Subgroup analysis showed consistent efficacy and safety across diverse laser platforms. Notably, FLACS exhibited no clear cost-effectiveness advantage over CPCS.