There is no consensus on the diagnosis or treatment policy for Preperimetric Glaucoma (PPG) because the pathogenesis of PPG is not clear at this time. Preperimetric Glaucoma Prospective Observational Study (PPGPS) is a first multicenter, prospective, observational study to clarify the pathogenesis of PPG. This article indicates study design, patient baseline characteristics, and analysis focused on optic nerve head (ONH) blood flow in PPG, as well as the intraocular pressure (IOP) -lowering effect and ONH blood flow-improving effects of Tafluprost.In this study, 122 eyes from 122 subjects (mean age: 53.1 ± 14.3) newly diagnosed as PPG were enrolled. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was evaluated with optical coherence tomography (OCT). The ONH blood flow was measured with laser speckle flowgraphy. The therapeutic effect of Tafluprost was evaluated at Month 0 (ONH blood flow-improving effect) and Month 4 (IOP-lowering effect).The untreated IOP, cpRNFLT, and baseline Mean deviation (MD) value was 16.4 ± 2.5 mmHg, 80.4 ± 8.2 μm, and -0.48 ± 1.29 dB, respectively. In the site-specific visual field evaluation using the sector map, there was no appreciable site-specific visual field defect in the eye with PPG. The inferior region of cpRNFLT in 4-quadrant OCT sector analysis and 6 o'clock region in 12-o'clock OCT sector analysis was the highest rate of abnormality in PPG eyes. Topical administration of Tafluprost significantly reduced IOP from 16.4 ± 2.5 mmHg at baseline to 14.5 ± 2.3 mmHg at Month 4 (P < 0.001, paired t-test). In the linear regression analysis, there was a significant relationship between the increase of ONH blood flow and baseline value.PPGPS is a first prospective study focusing on the pathology of PPG. This study is expected to elucidate the pathology of PPG, with evidence useful for determining a treatment strategy for PPG.