Aim: To evaluate the efficacy and safety of XEN® 45 gel stent implantation with a new surgical approach by ab externo transconjunctival technique. Materials and methods: A total of 31 eyes of 31 patients affected with primary open-angle glaucoma (POAG) were treated with an ab externo transconjunctival approach. All the XEN gel stent implantations were performed at the Department of Ophthalmology of the Hospital of San Severino Marche, AV3- Asur Marche, Macerata, Italy between January 2021 and May 2021, and the follow-up duration was at least 6 months. Results: A total of 31 eyes of 31 patients (mean age 65.6 ± 12.3 years; 20 males and 11 females) were included in the study. All the patients were affected by POAG. The mean intraocular pressure (IOP) was 25.3 ± 3.8 mm Hg, and the mean number of IOP-lowering topical medications before surgery was 2.7 ± 0.9. No intraoperative complications were reported. During the follow-up, one patient received medical treatment for a choroidal detachment, one patient had a 2 mm hyphema, and one patient had a partial migration of the stent in the anterior chamber. At the 1-month follow-up, the mean IOP was 12.8 ± 2.5 mm Hg and no patient was on IOP-lowering treatment, while at the 3-month and 6-month follow-ups, four patients were on treatment with one IOP-lowering drug. During the follow-up period, seven patients required postsurgical bleb needling, and one patient underwent a revision with PreserFlo® Microshunt implantation. The final mean IOP was 15.9 ± 2.7 mm Hg, and 27 out of 31 patients had an IOP of <18 mm Hg. Conclusion: Ab externo transconjunctival XEN® 45 gel stent implantation represents a safe and effective surgical treatment approach. Clinical significance: The ab externo approach represents a safe and effective technique, allowing early surgical timing and widening the group of patients who could benefit from the filtrating surgical technique before many years of topical medical treatment, which causes marked conjunctival alteration.