Purpose <p>To evaluate and compare the efficacy, safety, and two-years success rates of XEN^® 63 Gel Stent and PRESERFLO™ MicroShunt in uncontrolled glaucoma.</p> Methods <p>This retrospective study followed-up patients at day 1, week 1, and at month 1, 3, 6, 12, 18 and 24, post-operatively, reporting intraocular pressure (IOP), number of IOP lowering medications, success rates, and complications.</p> Results <p>Ninety-six patients were enrolled, 49 implanted with the Gel Stent (Group A) and 47 with the MicroShunt (Group B). Mitomycin C, at concentration of 0.02% and 0.04%, was applied in Group A and B, respectively. At two years, IOP reduced from 20.7 ± 3.8 to 13.3 ± 3.0 mmHg in Group A and from 21.7 ± 4.3 to 13.4 ± 2.4 mmHg in Group B (<i>p</i> &lt; 0.01). IOP reduction was comparable at all time points except for day 1 and week 1, where MicroShunt was slightly more effective (<i>p</i> &lt; 0.01 and 0.01). The mean number of medications dropped from 2.5 ± 1.0 to 0.8 ± 0.8 and from 2.7 ± 1.0 to 0.7 ± 1.0 in Group A and B, respectively. At two years, complete success was found in 38.7% and 40.4%, while qualified success in 85.7% and 78.7% in Group A and B, respectively. Bleb needling was more frequent in Group A than in Group B (<i>p</i> &lt; 0.01) (16 vs. 1 case), while bleb revisions were two-fold after MicroShunt implantation (10 vs. 5 cases) (<i>p</i> &lt; 0.01). Complications were comparable and self-limiting in both groups.</p> Conclusions <p>Over a 2-years follow-up, Gel Stent and MicroShunt presented comparable efficacy and safety in managing medically uncontrolled glaucoma.</p>