Purpose To evaluate the diagnostic efficacy of optical coherence tomography (OCT) angiography, in patients with pre-perimetric open-angle glaucoma. Methods Thirty-eight consecutive eyes of 26 patients with pre-perimetric open-angle glaucoma and 48 normal eyes of 32 controls were included in this prospective study. We evaluated OCT angiography, spectral-domain OCT and visual fields parameters. Differences between controls and patients and between OCT angiography parameters and traditional glaucoma measurements were evaluated. Receiver operating characteristic curves for OCT angiography parameters were assessed. Results The flow index ( p  = 0.021) and vessel density ( p  = 0.001) were significantly lower in pre-perimetric glaucoma eyes versus normal eyes. Ganglion cell complex parameters were significantly correlated to OCT angiography parameters ( p  < 0.05). Neither retinal nerve fiber layer (RNFL) nor visual field parameters correlated with OCT angiography parameters. Conclusions OCT angiography can be considered a reliable, easy-to-perform method with which to evaluate microvascular changes of optic nerve head for the early diagnosis and follow-up of glaucoma.