Long-lasting postoperative macular edema is a therapeutic challenge. The authors report an efficient combination therapy of oral mineralocorticoid receptor antagonists (eplerenone [Inspra; Pfizer, New York City, NY] or spironolactone, 25 mg/day to 50 mg/day) and topical dexamethasone (four times/day and progressive dose tapering) in three refractory cases following complex cataract or retinal detachment surgery. In Case 1, central macular thickness (CMT) decreased from 523 μm to 214 μm and visual acuity (VA) improved from 20/200 to 20/50 during a 6-month period. In Cases 2 and 3, CMT improved from 505 μm to 333 μm and from 438 μm to 316 μm during 5- and 3-month periods, respectively; however, VA remained unchanged (20/100 and 20/200) due to photoreceptor damage. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:936-942.].