Aim and objective: To report the incidence of late-onset endophthalmitis following XEN45® stent implantation. Background: Long-term safety profile and efficacy in relation to the so-called microinvasive glaucoma surgery (MIGS) techniques are still under evaluation. The XEN45® gel stent entails a bleb formation and often requires postoperative conjunctival management, differing from the current reviewed concept of minimally invasive procedures. Endophthalmitis has been described among the complications, triggered in the majority of cases by tube extrusion. Cases description: From our chart of 293 eyes operated on between November 2016 and November 2019, five (1.7%) patients developed endophthalmitis, which took place in the months 3, 4, 5, 11, and 14 after surgery, respectively. Sixty percent had undergone previous needling procedures. All of them showed a previous flat bleb and developed perforation of the conjunctiva caused by the distal portion of the tube. One patient was early eviscerated due to a fateful course. Treatment consisted of intravitreal, oral, and topical antibiotics, as well as topical corticosteroids. Eighty percent underwent device withdrawal, conjunctival gap suturing, anterior chamber washout, aqueous humor (AH) tab extraction (one positive for S. epidermidis and one for Streptococcus agalactiae), and pars plana vitrectomy. A second patient was eviscerated due to phthisis bulbi. Out of three remaining patients, one underwent vitrectomy for retinal detachment, while two patients required glaucoma surgery for intraocular pressure control. The final VA was ≤20/125 in all patients. Conclusion: The XEN45® device appears to trigger endophthalmitis by extruding the stent or unnoticed leakage through conjunctival defects. Special attention should be paid to flat and avascular blebs. Clinical significance: This series shows a higher rate of endophthalmitis (1.7%) compared with previous studies with a significant sample size (0.4–1.4%).