Purpose: To evaluate the 2-year treatment outcomes of the XEN gel stent (Allergan, Inc, Irvine, CA) in glaucoma patients. Design: Prospective, single-center interventional study. Participants: One hundred forty-nine eyes of 113 patients with open-angle glaucoma. Methods: Consecutive eyes with uncontrolled intraocular pressure (IOP) or signs of disease progression despite medical treatment were included to undergo either standalone XEN implantation or combined XEN implantation plus phacoemulsification surgery, both with mitomycin C injections. Main outcome measures: Primary efficacy outcome was success, defined as complete when the unmedicated IOP was 12 mmHg or less, 15 mmHg or less, or 18 mmHg or less and 20% lower than at baseline over the 2-year period and defined as qualified when the IOP fulfilled the same conditions with fewer medications than at baseline. Secondary measures were mean reduction in IOP and in the number of medications and the rates of reoperations. Results: One hundred nine eyes (84 patients; mean age, 74.3 years) underwent XEN plus phacoemulsification surgery and 40 eyes (29 patients; mean age, 74.7 years) underwent standalone XEN surgery. Overall, 129 eyes (86.6%; 96 eyes of 75 XEN plus phacoemulsification patients and 33 eyes of 24 XEN standalone surgery patients) completed the study. Mean medicated IOP was 20.0±7.5 mmHg at baseline and 14.1±3.7 mmHg at 2 years (P < 0.01), a 29.3% IOP reduction. Mean number of medications dropped from 2.0±1.3 before surgery to 0.6±0.9 at 2 years (P < 0.001). Complete success was achieved in 18.2% of eyes using the 12 mmHg or less and 20% reduction criteria and in 44.4% using the 15 mmHg or less threshold. Needling with mitomycin C was performed in 58 eyes (45%). In all, 11.4% underwent reoperations. Conclusions: After 2 years, XEN gel stent surgery achieved a clinically and statistically significant reduction both in IOP and the number of antiglaucoma medications, while requiring a high rate of needling interventions.