Purpose. To evaluate the long-term efficacy and safety of the iStent inject device (Glaukos Corporation, Laguna Hills, CA) combined with phacoemulsification in patients with coexistent cataract and open-angle glaucoma or ocular hypertension (OHT). Methods. A prospective, uncontrolled, nonrandomized, interventional case series study was conducted in patients with both mild or moderate open-angle glaucoma or OHT and cataract. Patients underwent cataract surgery along with the implant of two iStent inject devices. Outcome measures were intraocular pressure (IOP), topical hypotensive medications required, and best-corrected visual acuity (BCVA). Results. 20 patients were enrolled. Mean follow-up was 47.4±18.46 months. Mean baseline IOP was 19.95±3.71 mmHg with medication and 26±3.11 mmHg after washout. Mean end-follow-up IOP was 16.25±1.99 mmHg, representing an IOP decrease of 36.92%, 9.74±3.14 mmHg (P<0.001), from baseline washout IOP. The mean number of medications was significantly reduced from 1.3±0.66 to 0.75±0.79 (P=0.017). 45% of patients were medication-free by the end of follow-up. Mean log⁡MAR BCVA improved significantly from 0.42±0.16 to 0.18±0.16 (P<0.001). No complications of surgery were observed. Conclusion. The iStent inject device combined with cataract surgery served to significantly reduce both IOP and medication use in the long term in patients with coexistent open-angle glaucoma or ocular hypertension (OHT) and cataract.