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To characterize the natural history and define the risk factors associated with the progression of normal-tension glaucoma (NTG) in Japanese patients who were followed up closely without treatment. Prospective 5-year study. Patients with NTG with intraocular pressure (IOP) consistently ≤15 mmHg without treatment at baseline. Visual field (VF) examinations were performed every 3 months, and disc/peripapillary retina photographs were taken every 6 months. Patients were followed up without treatment. Deterioration in VF was defined by reference to Guided Progression Analysis Software of the Humphrey VF Swedish Interactive Thresholding Algorithm 24-2 (Carl Zeiss Meditec, Jena, Germany) and disc/peripapillary retina deterioration as adjudged by 3 independent observers. Life table analysis was used for evaluating the time to disease progression, as defined by VF or deterioration of the optic nerve head structure. The Cox proportional hazards model was used to identify risk factors for glaucoma progression. We enrolled 90 patients (mean age, 53.9 years; baseline IOP, 12.3 mmHg; mean deviation [MD], −2.8 decibels [dB]). The MD slope averaged −0.33 dB/year (median, −0.23; 95% confidence interval [CI], −0.44 to −0.22). Glaucoma progression probability at 5 years was 66% (95% CI, 55–78), as defined by VF deterioration or disc/peripapillary retina deterioration (criterion 1): 52% (95% CI, 37–60), as defined by VF deterioration (criterion 2), and 50% (95% CI, 38–71), as defined by disc/peripapillary retina deterioration (criterion 3). Presence or history of disc hemorrhage (DH) (P < 0.001), long-term IOP fluctuation (P = 0.020), and a greater vertical cup-to-disc ratio (v-C/D) (P = 0.018) were significant predictors for progression defined by criterion 1. Long-term IOP fluctuation (P = 0.011) and a greater v-C/D (P = 0.036) were significant predictors for progression by criterion 2. Presence or history of DH (P = 0.0018) and long-term IOP fluctuation (P = 0.022) were significant predictors for progression by criterion 3. In Japanese patients with NTG with mean baseline IOP of 12.3 mmHg without treatment, estimated mean MD slope for 5 years was –0.33 dB/year; probability of glaucoma progression based on VF or disc/peripapillary end points at 5 years was 66%. Presence or history of DH, long-term IOP fluctuation, and greater v-C/D significantly contributed to progression. [ABSTRACT FROM AUTHOR]