PURPOSE: To evaluate the effect of oral spironolactone and eplerenone, two specific antagonists of the mineralocorticoid receptor, in central serous chorioretinopathy (CSCR). METHODS: In this prospective, placebo-controlled trial, sixty patients with persistent CSCR were assigned to three treatment group. Twenty patients in Group 1 were treated with 25 mg of spironolactone (Aldactone; Pfizer) for 1 week, then increased to 50 mg for the following 3 weeks, then shifted to eplerenone 50 mg for 1 month. Twenty patients in Group 2 were treated with 25 mg of eplerenone (Inspra; Pfizer) for 1 week, then increased to 50 mg for the following 3 weeks, and then shifted to spironolactone 50 mg for 1 month. Twenty patients in Group 3 were treated with 1 placebo control tablet for 1 week, then increased to two tablets for the following 3 weeks, and then shifted to spironolactone 50 mg for 1 month. At the end of the second month, all the treatments were stopped, and the patients were followed for two additional months. Primary outcome measure was a change in BCVA at 1, 2, and 4 months. Secondary outcome was a change of >20 % in the size of SRF recorded with OCT at 1, 2, and 4 months of treatment. RESULTS: In terms of BCVA, treatment in Group 1 was effective from the first month (spironolactone, p value 0.01), and in Group 2 effective from the second month (shift to spironolactone, p value 0.004). Since the p value after the first month was 0.2 in Group 2, even with a larger sample, it would be difficult to see an efficacy of an eplerenone treatment after 1 month. As for the SRF, both in Group 1 and Group 2, both treatments were found to be equally effective after 1 month of administration (p values 0.004). At 4 months, only in Group 3, there was no statistical improvement of BCVA and SRF (p values 0.09 and 0.5). CONCLUSIONS: Spironolactone is statistically superior to eplerenone in improving BCVA of patients with CSCR, while both drugs can be considered equally effective in promoting the reabsorption of SRF.