Background Chorioretinopathy centralis serosa (CCS) is a common disease that leads to the loss of retinal ion/fluid homeostasis due to decompensation of the retinal pigment epithelium, resulting in fluid accumulation with detachment of the neurosensory retina and/or retinal pigment epithelium. We investigated the effect of eplerenone, a mineralocorticoid receptor inhibitor, on chronic recurrent CCS (cr-CCS). Methods A retrospective study with data analysis of 17 eyes (12 patients) between 2014 2021 with cr-CCS in whom other methods were not effective, not applicable, or not desired, was performed. Duration of CCS was at least 12 months with at least one recurrence. Each patient received 25mg (1st week) and 50mg (from the 2nd week) for at least 3 months. In each case, best-corrected visual acuity and central and peripheral retinal thickness were measured by spectral-domain optical coherence tomography. Side effects were rated by the patients as "none", "mild" (noticeable but not affecting), "tolerable" (affecting but acceptable because of good effect), and "not tolerable" (then discontinuation of therapy). Results There was no significant reduction in central or peripheral retinal thickness. A complete reduction of subretinal fluid was achieved in 5 of 17 eyes (29.4%). In 12 eyes, no effect of eplerenone could be detected, so other therapies were required. Visual acuity change was mainly dependent on the duration of CCS and the degree of photoreceptor damage. Side effects were reported by 11 patients as "none" and 1 patient as "mild" (arterial hypotension). No other side effects were observed. Conclusion The response rates of therapy with eplerenone were relatively low, and no significant effect could be demonstrated. Eplerenone should not (no longer) be routinely used in the therapy of cr-CCS.