To evaluate 2-year safety and effectiveness of iStent inject ® W implantation with phacoemulsification in adult Japanese open-angle glaucoma (OAG) patients. Multicenter, prospective, post-market surveillance. Eyes were evaluated preoperatively and at Day 1, Week 1, and Months (M) 1, 3, 6, 12, and 24. Primary outcome was M24 cumulative probability of success defined as no additional glaucoma surgery and intraocular pressure (IOP) < preoperative value and number of glaucoma medications ≤ preoperative value or IOP ≤ preoperative value and number of glaucoma medications < preoperative value. Other endpoints included cumulative probability of achieving American Academy of Ophthalmology Glaucoma (AAO) success criteria for minimally invasive glaucoma surgery with phacoemulsification, and changes in mean IOP, number of glaucoma medications, and medication costs over time. Subanalysis was based on OAG subtype [primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and exfoliative glaucoma (XFG)]. Adverse events were recorded. Cumulative probability of success at M24 was 91.7%, 98.8%, 88.9%, and 85.0% for cohort (N = 214), NTG, XFG, and POAG, respectively. The AAO M24 success was 80.7%. Statistically significant reductions in mean IOP and number of medications were observed through M24 in cohort and OAG subtypes. At M24, the estimated reductions in mean (standard error) IOP and number of medications were 2.0 (0.5) mmHg and 1.9 (0.4), respectively, in the cohort. Adverse events were minimal. At M24, the average monthly glaucoma medication costs decreased by 49.7%. Japanese OAG eyes treated with iStent inject W combined with phacoemulsification experienced reduced IOP and medication burden with minimal adverse events and high success rates over postoperative 2 years.