OBJECTIVE Clinical outcomes of biaxial microincision versus coaxial small incision cataract surgery were compared in a prospective, controlled, paired-eye clinical study. METHODS A total of 84 eyes of 42 patients underwent cataract surgery using the biaxial microincision (B-MICS) technique in either the right or left eye. The fellow eye was to undergo cataract surgery using the standard coaxial small incision (SICS) technique. All surgeries were performed using the Stellaris Vision Enhancement System and all eyes were implanted with an aspheric microincision intraocular lens (IOL). The 1.2-mm B-MICS incision was widened to 1.8 mm for IOL insertion. The main outcome measure was the change from baseline best-corrected visual acuity (BCVA). Secondary outcome measures were uncorrected visual acuity (UCVA), surgically induced astigmatism (SIA), manifest subjective refraction in spherical equivalent (MRSE), absolute phacoemulsification time (APT), effective phacoemulsification time (EPT), mean phacoemulsification power, and endothelial cell count (ECC). Follow-up was at 1 day, 3 days, 1 week, and 2 months. RESULTS The treatment groups did not differ in baseline characteristics. Improvement in BCVA over baseline logarithm of the minimum angle of resolution (logMAR) was statistically significantly greater with B-MICS than SICS at 1 day (B-MICS -0.1, SICS -0.05; 95% CI -0.26 to -0.05, p=0.005). Mean improvement in UCVA from baseline was greater with B-MICS at 1 day (B-MICS -0.33, SICS -0.12; 95% CI -0.35 to -0.10, p=0.001), 3 days (B-MICS -0.39, SICS -0.26; 95% CI -0.22 to -0.02, p=0.022), 1 week (B-MICS -0.44, SICS -0.33; 95% CI -0.20 to -0.009, p=0.033), and 2 months (B-MICS -0.47, SICS 0.38; 95% CI -0.19 to +0.002, p =0.054). At 2 months, SIA was significantly lower with B-MICS than SICS (B-MICS 0.70 D, SICS 0.89 D; 95% CI -0.39 to -0.1, p=0.045), as was endothelial cell loss (B-MICS -1.4%, SICS -7.8%; p=0.05). The EPT was lower with B-MICS (B-MICS 1.60 s, SICS 2.80 s; 95% CI -1.68 to -0.77, p<0.001) with no difference in mean phaco power. CONCLUSIONS Compared to the standard small incision technique, B-MICS showed earlier improvement in BCVA, better overall UCVA, less SIA, and less endothelial cell loss.