AIM: To examine eplerenone (Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy (CSCR). METHODS: A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit, spectral domain optical coherence tomography (SD-OCT) imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy. RESULTS: A total of 17 eyes of 13 patients treated with 25 and 50 mg of oral eplerenone per day were identified. Subretinal fluid (SRF) decreased over time following eplerenone therapy (P= 0.007 and P = 0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 μm at baseline to 15.3 μm at day 181+. SRF diameter decreased from an average of 2174.4 μm at baseline to 46.9 μm at day 181+. LogMAR visual acuity improved from 0.42 (Snellen equivalent: 20/53) at baseline to 0.29 (Snellen equivalent: 20/39) at day 181+ (P = 0.024). Central subfield thickness (CST) decreased from 339.5 μm at baseline to 270.3 μm at day 181+ (P = 0.029). CONCLUSION: Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR.