Purpose: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with an elevated risk of cardiovascular events, which can be linked to endothelial dysfunction. In this study, we aimed to investigate whether noninvasive ventilation (NIV) acutely changes endothelial function in hospitalized AECOPD patients. Methods: Twenty-one AECOPD patients were assessed in a hospital ward setting from 24 to 48 h after admission. NIV was applied using a ventilator with bilevel pressure support. Before and after NIV protocol, patients were evaluated regarding (1) endothelium-dependent function, assessed non-invasively using the flow-mediated dilation (FMD) method; (2) arterial blood gas analysis. Other baseline evaluations included clinical and anthropometric data, and laboratory tests. Results: The total group showed a significant improvement in FMD as a result of NIV effect (P = 0.010). While arterial carbon dioxide and oxygen were not altered, oxygen saturation increased after NIV (P = 0.045). The subgroup comparison of responders (FMD ≥ 1%) and non-responders (FMD < 1%) showed significant baseline differences in body mass index (BMI) (P = 0.019) and predicted forced expiratory volume in one second (FEV1) (P = 0.007). In univariate and multivariate analyses, both BMI and FEV1 were determinant for endothelial response to NIV. Conclusion: NIV acutely improves endothelial function in hospitalized AECOPD patients. Overweight and COPD severity may represent important characteristics for the magnitude of peripheral vascular response.