Abstract: Objective To assess the safety and efficacy of the iStent trabecular micro-bypass stent (Glaukos Corporation, Laguna Hills, CA) in combination with cataract surgery in subjects with mild to moderate open-angle glaucoma. Design Prospective, randomized, open-label, controlled, multicenter clinical trial. Participants A total of 240 eyes with mild to moderate open-angle glaucoma with intraocular pressure (IOP) ≤24 mmHg controlled on 1 to 3 medications were randomized to undergo cataract surgery with iStent implantation (treatment group) or cataract surgery only (control). Fifty additional subjects were enrolled to undergo cataract surgery with iStent implantation under protocol expansion. Data in this report are based on the first 240 eyes enrolled. Intervention Implantation of the iStent trabecular micro-bypass stent in conjunction with cataract surgery or cataract surgery only. Main Outcome Measures The primary efficacy measure was unmedicated IOP ≤21 mmHg at 1 year. A secondary measure was unmedicated IOP reduction ≥20% at 1 year. Safety measures included best-corrected visual acuity (BCVA), slit-lamp observations, complications, and adverse events. Results The study met the primary outcome, with 72% of treatment eyes versus 50% of control eyes achieving the criterion ( P P = 0.003). The overall incidence of adverse events was similar between groups with no unanticipated adverse device effects. Conclusions Pressure reduction on fewer medications was clinically and statistically significantly better 1 year after stent plus cataract surgery versus cataract surgery alone, with an overall safety profile similar to that of cataract surgery alone. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.