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To evaluate the macular thickness, choroidal thickness, and visual acuity changes in eyes of patients with bilateral chronic central serous chorioretinopathy during eplerenone treatment.This prospective clinical trial was conducted on patients with bilateral chronic central serous chorioretinopathy, who had subretinal fluid (SRF) in 1 eye. Twenty-eight patients were treated with 50 mg/day of oral eplerenone for 3 months and were observed for another 3 months. Twenty-eight eyes with SRF were compared with the 28 fellow eyes with pachychoroid pigment epitheliopathy.The central macular and choroidal thickness showed a significant decrease (P < 0.005) at 3 months in all eyes, but change in choroidal thickness was smaller in nonexudative fellow eyes (P > 0.05 at 6 months). In the exudative eyes, the decrease in choroidal thickness showed a significant correlation with the resolution of SRF (P < 0.001). Visual acuity remained stable in all eyes, with significant improvement only in exudative eyes at 6 months (P < 0.005). Baseline choroidal thickness was a significant positive predictor for SRF decrease (P = 0.003).Patients with chronic central serous chorioretinopathy can safely be treated with eplerenone as it can reverse choroidal vasodilation with an accompanying resolution of the SRF and improvement in visual acuity. These beneficial therapeutic effects are more pronounced in the exudative eyes.