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Background The present study reports a multicenter experience of using hydrophilic polymer-coated (HPC) flow diverters (FDs) with prasugrel single antiplatelet therapy (SAPT) to treat posterior circulation aneurysms (PCAs).Methods A prospectively maintained database was retrospectively reviewed to identify all cases of intracranial PCA treated with HPC-coated FDs under SAPT (prasugrel). The clinical presentation and outcomes, periprocedural and postprocedural complications, and degree of occlusion at follow-up (FU) were evaluated.Results A total of 74 patients were treated (45.9% female). Ischemic complications were experienced by two patients (2.7%) and were dependent on the use of FDs. No cases of aneurysm rupture or hemorrhagic complications related to antiplatelet therapy or the FD treatment were recorded. The rate of complete occlusion was 77.9% in the early FU period (3–6 months) and 90.3% in the initial 12-month period.Conclusion In this single-arm retrospective study, HPC-coated FDs with prasugrel SAPT were associated with high safety in the treatment of ruptured and unruptured PCA and high occlusion rates at early- and mid-term FU.