Abstract Heads-up three-dimensional (3D) surgical visualization systems allow ophthalmic surgeons to replace surgical microscope eyepieces with high-resolution stereoscopic cameras transmitting an image to a screen. We investigated the effectiveness and safety of the heads-up NGENUITY 3D Visualization System in a retrospective evaluation of 241 consecutive vitreoretinal surgeries performed by the same surgeon using conventional microscopy (CM group) over a 1-year period versus the NGENUITY System (3D group) over a consecutive 1-year period. We included for study vitreoretinal surgeries for treatment of retinal detachment (RD) (98 surgeries), macular hole (MH) (48 surgeries), or epiretinal membrane (ERM) (95 surgeries). A total of 138 and 103 eyes were divided into 3D and CM groups, respectively. We found no differences in 3-month postoperative rates of recurrence of RD (10% versus 18%, p = 0.42), MH closure (82% versus 88%, p = 0.69), or decrease in central macular thickness of ERMs (134 ± 188 µm versus 115 ± 105 µm, p = 0.57) between the 3D and CM groups, respectively. Surgery durations and visual prognosis were also similar between both groups. We consolidate that the NGENUITY System is comparable in terms of visual and anatomical outcomes, giving it perspectives for integration into future robotized intervention.