During flow diversion, the choice of the length, diameter, and location of the deployed stent are critical for the success of the procedure. Sim&Size software, based on the three-dimensional rotational angiography (3D-RA) acquisition, simulates the release of the stent, suggesting optimal sizing, and displaying the degree of the wall apposition. Objective To demonstrate technical and clinical impacts of the Sim&Size simulation during treatment with the Pipeline Flex Embolization Device. Methods Consecutive patients who underwent aneurysm embolization with Pipeline at our department were retrospectively enrolled (January 2015–December 2017) and divided into two groups: treated with and without simulation. Through univariate and multivariate models, we evaluated: (1) rate of corrective intervention for non-optimal stent placement, (2) duration of intervention, (3) radiation dose, and (4) stent length. Results 189 patients, 95 (50.2%) without and 94 (49.7%) with software assistance were analyzed. Age, sex, comorbidities, aneurysm characteristics, and operator’s experience were comparable among the two groups. Procedures performed with the software had a lower rate of corrective intervention (9% vs 20%, p=0.036), a shorter intervention duration (46 min vs 52 min, p=0.002), a lower median radiation dose (1150 mGy vs 1558 mGy, p<0.001), and a shorter stent length (14 mm vs 16 mm, p<0.001). Conclusions In our experience, the use of the virtual simulation during Pipeline treatment significantly reduced the need for corrective intervention, the procedural time, the radiation dose, and the length of the stent.