PURPOSE: To compare the efficacy and safety outcomes of bimanual microincision cataract surgery (MICS) versus 2.2-mm coaxial phacoemulsification assisted by Femtosecond LenSx (Alcon-LenSx Inc., Aliso Viejo, CA). METHODS: This prospective, randomized, observational, comparative case series comprised 50 cataractous eyes of 50 patients receiving femtosecond laser refractive lens surgery followed by a bimanual MICS technique with two 1-mm incisions (25 patients) (FemtoMICS group) and a coaxial phacoemulsification technique with a 1-mm paracentesis and a 2.2-mm principal incision (25 patients) (FemtoCoaxial group). The main outcomes measures were: ultrasound power, effective phacoemulsification time, postoperative spherical equivalent, higher-order aberrations (corneal and internal), corneal thickness, endothelial cell count, macular thickness, and complications during and after surgery. Both groups were absolutely comparable for all variables preoperatively. RESULTS: Mean ultrasound power was 1.8% ± 0.9% for MICS and 14.7% ± 4.9% for 2.2-mm incisions (P .001). Effective phacoemulsification time values for MICS and 2.2-mm incisions were 1.5 ± 0.9 and 4.5 ± 2.9 sec, respectively (P = .002). Mean postoperative spherical equivalent was -0.26 for FemtoMICS and -0.33 for FemtoCoaxial (P > .05). The efficacy index at 1 month postoperatively was 160.2% for FemtoMICS and 149% for FemtoCoaxial. No significant differences were found in corneal thickness, endothelial cell count, and macular thickness. Complications included posterior capsule rupture (4%) and anterior capsule rupture with no posterior capsule tear (4%) for FemtoMICS and bridges due to incomplete capsulorhexis (4%) for FemtoCoaxial. CONCLUSIONS: MICS and coaxial phacoemulsification techniques assisted by the Femtosecond LenSx achieved excellent safety and efficient outcomes. The FemtoMICS technique was surgically and statistically more efficient than the FemtoCoaxial technique.