Aim: This meta-analysis explores the efficacy and adverse event profile of the iStent, an ab interno implant for the treatment of open-angle glaucoma. Methods: A systematic literature search of Ovid MEDLINE and EMBASE was used to identify peer-reviewed original studies that provided efficacy data on the first or second generation iStent for at least five eyes. Intraocular pressure (IOP) was the primary efficacy endpoint, while the number of medication classes was the secondary outcome. Weighted mean differences were reported for continuous endpoints, while a relative risk was computed for dichotomous variables. Review Results: The search revealed 545 results, of which 1767 eyes from 28 studies were included. The cohort age was 71.4 ± 5.4 years, and 44.9% of patients were male. There was a significantly greater IOP reduction after the use of two first-generation stents compared to one, irrespective of phacoemulsification status (p < 0.001). Additionally, there was a significantly greater IOP reduction following iStent alone relative to phaco-iStent for the first-generation iStent (p < 0.001) and the iStent inject (p < 0.001). For the first generation stent, combined phaco-iStent provided a greater level of IOP reduction (p < 0.001) and reduction in the number of medication classes relative to phacoemulsification alone (p < 0.001). In total, 22.5% of eyes that received iStent implantation sustained some type of adverse event. The most common adverse events were intraocular pressure elevation, stent blockage or obstruction, stent malposition and hyphema. Conclusion and Clinical Significance: Statistically significant differences in efficacy outcomes exist between different numbers of stents and the presence or absence of concurrent phacoemulsification.