Purpose The aim of this study was to evaluate whether XEN® implantation is a reasonable and safe method to lower the intraocular pressure (IOP) and amount of medication for adult primary open-angle glaucoma (POAG) over a 3-year period. The influence of the type of anesthesia, previous glaucoma surgery, and postoperative interventions on the outcome were examined. Methods In this retrospective study, 96 eyes were included. XEN® implantation was performed as sole procedure under general (n = 86) or local anesthesia (n = 10). IOP and number of glaucoma medication were assessed preoperatively: day 1, week 6, month 3, 6, 12, 24, and 36. Further outcome parameters were Kaplan-Meier success rates, secondary intervention, and complication rates. Results IOP decreased from 20.7 ± 5.1 to 12.8 ± 2.5 mmHg at the 36-month follow-up (p < 0.001) and glaucoma therapy was reduced from 3.3 ± 0.8 to 1.2 ± 1.6 (36 months, p < 0.001). Transient postoperative hypotony was documented in 26 eyes (27.1%). General anesthesia resulted in a significant improvement of the survival rate compared to local anesthesia (77% vs. 50%, p = 0.044). Prior iStent inject®, Trabectome®, or SLT laser had no significant impact, such as filter bleb revision. The number of postoperative needlings had a significantly negative influence (p = 0.012). Conclusion XEN® implantation effectively and significantly lowers the IOP and number of glaucoma therapy in POAG in the 36-month follow-up with a favorable profile of side effects and few complications. In case of IOP, general anesthesia has a significant positive influence on the survival rate, whereas prior SLT or MIGS does not have significant impact.