© 2017 Elsevier Inc. Background Stent-assisted coil embolization and flow diversion with the Pipeline embolization device (PED) are both effective endovascular treatment options for ophthalmic segment aneurysms (OSAs) of the internal carotid artery. Here we present a large comparative cohort study. Methods A multicenter, retrospective cohort comparison study of consecutively treated OSAs was conducted at 2 academic institutions in the United States comparing stent-coiling (between 2007 and 2015) and PED (between 2011 and 2016). Results A total of 62 of OSAs were treated with stent-coiling and 106 were treated with the PED. The stent-coiling–treated aneurysms were larger, although the maximum diameter was not significantly different between the 2 groups (P = 0.05). The median duration of follow-up was 22.5 months for the stent-coiling group and 8.7 months for the PED group (P = 0.0002). Complete occlusion at last follow-up was achieved in 75.9% of aneurysms in the stent-coiling group and in 81.1% of aneurysms in the PED group (P = 0.516). The retreatment rate was higher with stent-coiling, but the difference did not reach statistical significance (P = 0.062). A good functional outcome was achieved in 96.6% of patients in the stent-coiling group and in 94.7% of those in the PED group (P = 0.707). The rate of neurologic complications was 4.8% in the stent-coiling group and 9.4% in the PED group (P = 0.376). Conclusion Stent-coiling and the PED were equally effective for treating OSAs. There were no significant differences in terms of procedural complications, angiographic, functional, and visual outcomes. PED may be more favorable for multiple adjacent OSAs.