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Background: Controversy exists regarding the optimum number of flow diverters for the treatment of intracranial aneurysms. We explored the effect of the number of Pipeline embolization devices (PEDs; Medtronic, Dublin, Ireland) deployed on rates of aneurysm occlusion and complications. Methods: Consecutive patients who underwent saccular intracranial aneurysm treatment solely with the PED were included in this retrospective study. Computed tomographic, magnetic resonance, or digital subtraction angiographic images at 6 and 12 months and last follow-up (>12 months) were reviewed for aneurysm occlusion. Complication and retreatment rates were recorded and analyzed statistically. Results: The study included 141 aneurysm treatments in 119 patients. A single PED was deployed in 105 cases, two PEDs in 31 cases, and three PEDs in 5 cases (total = 182 devices). Six-month angiographic data were available for 103 patients. Occlusion rates were 67.1% for single-PED cases and 90.0% for cases with > 1 PED (p = 0.028). The 12-month occlusion rate (follow-up available for 132) for single-PED cases was 74.7% compared to 91.7% for multiple-PED cases (p = 0.04). On multivariate analysis, number of PEDs was an independent predictor of aneurysm occlusion at 12 months (odds ratio 6.3, 95% confidence interval 1.8–22.8, p = 0.005). Thromboembolic complication rates were the same in the single- and multiple-PED treatment groups (2.8%). The retreatment rate was higher in patients treated with a single PED (16.2% vs. 0%, p = 0.01). Conclusions: Deployment of > 1 Pipeline embolization device was associated with higher intracranial aneurysm occlusion and lower retreatment rates. No significant difference was found in complication rates. [ABSTRACT FROM AUTHOR]