The Sim&Size software simulates case-specific intraluminal Pipeline Embolization Device behavior, wall apposition, and device length in real-time on the basis of rotational angiography DICOM data. The purpose of this multicenter study was to evaluate whether preimplantation device simulation with the Sim&Size software results in selection of different device dimensions than manual sizing. Materials and methods: In a multicenter cohort of 74 patients undergoing aneurysm treatment with the Pipeline Embolization Device, we compared apparent optimal device dimensions determined by neurointerventionalists with considerable Pipeline Embolization Device experience based on manual 2D measurements taken from rotational angiography with computed optimal dimensions determined by Sim&Size experts blinded to the neurointerventionalists' decision. Agreement between manually determined and computed optimal dimensions was evaluated with the Cohen κ. The significance of the difference was analyzed with the Wilcoxon signed rank test. Results: The agreement index between manual selection and computed optimal dimensions was low (κ for diameter = 0.219; κ for length = 0.149, P < .01). Computed optimal device lengths were significantly shorter (median, 14 versus 16 mm, T = 402, r = -0.28, P < .01). No significant difference was observed for device diameters. Conclusions: Low agreement between manually determined and computed optimal device dimensions is not proof, per se, that virtual simulation performs better than manual selection. Nevertheless, it ultimately reflects the potential for optimization of the device-sizing process, and use of the Sim&Size software reduces, in particular, device length. Nevertheless, further evaluation is required to clarify the impact of device-dimension modifications on outcome.