The Pipeline Embolization Device (PED) is reported to be a safe treatment tool for aneurysms. However, mortality occurs in a few cases, and this has not been clearly studied. We conducted a multicenter study to retrospectively evaluate the causes of, and risk factors for, mortality in patients with intracranial aneurysms treated with the PED. We retrospectively reviewed the prospectively maintained databases of patients with intracranial aneurysms treated by PED placement at 14 academic institutions from 2014 to 2019. Patients' data, including clinical and radiographic information, were analyzed with an emphasis on mortality-related complications. A total of 1171 consecutive patients underwent 1319 PED procedures to treat 1322 intracranial aneurysms. The mortality rate was 1.5% (17/1171), and in 1.3% of the patients (15/1171), deaths were caused by delayed aneurysmal rupture, distal intraparenchymal hemorrhage, and neurological compression symptoms associated with PED procedures. Multivariate analysis showed that previous treatment (OR, 12.657; 95% CI, 3.189 to 50.227; P<0.0001), aneurysm size ≥10 mm (OR, 4.704; 95% CI, 1.297 to 17.068; P=0.019), aneurysm location (basilar artery) (OR, 10.734; 95% CI, 2.730 to 42.207; P=0.001), and current subarachnoid hemorrhage (OR, 4.505; 95% CI, 0.991 to 20.474; P=0.051) were associated with neurological complications resulting in mortality. Delayed aneurysm rupture, distal intraparenchymal hemorrhage, and neurological compression were the main causes of mortality in patients with intracranial aneurysms treated with the PED. Large basilar aneurysms are associated with an increased risk of postoperative death and require increased attention and caution. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.