Background: Optical coherence tomography (OCT) angiography is a new method to assess the density of the vascular networks. Vascular abnormalities are considered involved in multiple sclerosis (MS) pathology. Objective: To assess the presence of vascular abnormalities in MS and to evaluate their correlation to disease features. Methods: A total of 50 MS patients with and without history of optic neuritis (ON) and 46 healthy subjects were included. All underwent spectral domain (SD)-OCT and OCT angiography. Clinical history, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS) and disease duration were collected. Results: Angio-OCT showed a vessel density reduction in eyes of MS patients when compared to controls. A statistically significant reduction in all SD-OCT and OCT angiography parameters was noticed both in eyes with and without ON when compared with control eyes. We found an inverse correlation between SD-OCT parameters and MSSS (p = 0.003) and between vessel density parameters and EDSS (p = 0.007). Conclusion: We report a vessel density reduction in retina of MS patients. We highlight the clinical correlation between vessel density and EDSS, suggesting that angio-OCT could be a good marker of disease and of disability in MS.