Purpose To retrospectively evaluate the short-term efficacy of omidenepag isopropyl (EYBELIS 0.002%) by assessing its intraocular pressure (IOP)-lowering capability and safety in patients with normal-tension glaucoma (NTG). Patients and Methods Fifty-four NTG patients (54 eyes) who were newly administrated with omidenepag isopropyl were enrolled in the study. The subjects comprised 22 men and 32 women, and the mean age of the subjects was 55.0 ± 14.1 years. The mean deviation value using the Humphrey visual field test program (30–2 SITA Standard) was −5.03 ± 3.38 dB. The following data were retrieved from the medical records and used for retrospective analyses: IOP at baseline 1–2 months and 3–4 months after administration. The frequency of non-responder patients who had less than 10% IOP reduction was evaluated. Patients were observed for adverse reactions and dropouts at each time point. Results IOP at baseline, after 1–2 months and after 3–4 months was 15.7 ± 2.6 mmHg, 13.5 ± 2.3 mmHg, and 13.6 ± 2.4 mmHg, respectively. There was a significant decrease in IOP after administration (p<0.0001). Eleven patients (22.4%) were non-responders. Adverse reactions occurred in 4 patients (7.4%), including conjunctival hyperemia in 3 patients (after 1 week, 2 weeks, and 1 month, respectively) and eye pain in 1 patient (after 1 month). Five patients (9.3%) dropped out of the study because of an adverse reaction in 3 patients, insufficient IOP reduction in 1 patient, and discontinuation of follow-up of 1 patient at our institution. Conclusion After administration of omidenepag isopropyl, IOP in patients with NTG was significantly decreased. However, adverse reactions occurred in 7.4% of patients.