Background and purpose While drug-eluting stents (DES) have been widely applicated in coronary stenosis, uncertainty persists concerning the relative performance and clinical benefit in patients undergoing vertebral artery stenting when compared with a bare metal stent (BMS). We sought to compare in-stent restenosis (ISR) rates of DES and BMS in the treatment of vertebral artery ostium (VAO) stenosis. Materials and Methods This study analyzed a single-center prospective cohort. Over 1.5-year period (January 2014-June 2015), 137 consecutive patients underwent VAO stenting involving deployment of 76 DES and 74 BMS. Patient demographics, comorbidities, stenosis severity, stent diameters and lengths, periprocedural complications, imaging and duplex ultrasonography follow-up and recurrent symptoms were assessed. Results Technical success was achieved in all patients. Mean VAO stenosis at presentation were 82.4 ± 7.2% in the DES group and 83.3 ± 7.5% in the BMS group and were reduced to 12.5 ± 4.5% and 11.3 ± 4.0%. Mean stent diameter was 3.53 ± 0.40 mm in DES and 5.05 ± 0.40 mm in BMS (p < 0.0001). Mean follow-up was 12.3 months for DES and 11.7 months for BMS. The use of DES was associated with significant lower ISR rates compared with BMS (18.4% vs. 31.1%; OR = 2.628, p = 0.021). Recurrent symptoms rates were similar in DES vs. BMS (2.6% vs 2.7%, p = 0.680). Stent type and stent diameter were independent risk factors for ISR (P = 0.026). Conclusion Our results suggest superior efficacy of deploying DES for the treatment of VAO stenosis with lower ISR rates as compared to BMS, but do not support significant differences in periprocedural risk and recurrent symptoms rate.