Aim To develop an approach based on targeted gene capture and next-generation sequencing to determine the genetic defects in patients with abdominal aortic aneurysm precisely and effectively and confirm the role of fibrillin-1 （FBN1） in the pathogenesis of abdominal aortic aneurysm. Methods We analyzed four abdominal aortic aneurysm patients. Peripheral blood was collected and genomic DNA was isolated. FBN1 were selected by a gene capture strategy, using GenCap custom enrichment kit. The enrichment libraries were sequenced on Illumina HiSeq 2000 sequencer for paired read 90 bp to determine the mutation frequency in FBN1. Variants which have been reported in dbSNP137 or 1000 genome and in-house database were filtered. Selected variants were further validated by PCR and Sanger sequencing. Results For the samples subjected to targeted next-generation sequencing, the average sequencing depths on the targeted regions were yielded from 448.15 to 536.61. Meanwhile, coverage of targeted exons were ranged from 99.5% to 99.7%. We identified one missense mutation in FBN1: c.2753 C＞G （p.Pro918Arg）, which was validated by Sanger sequencing. Conclusions Our results confirm the role of FBN1 in the pathogenesis of abdominal aortic aneurysm and demonstrated the robustness of targeted next-generation sequencing to precisely and rapidly determine genetic defects.