AIM: To compare the effectiveness of combined fenofibrate and spironolactone with fenofibrate alone for treatment of central serous chorioretinopathy (CSCR). METHODS: Totally 60 patients (60 eyes) with a history of acute CSCR were randomed into two groups: group A with combination of fenofibrate (200 mg) and spironolactone (100 mg), and group B with only fenofibrate (200 mg). They were taken half an hour before meals and once per day for 8wk. The changes of the visual acuity, subjective symptom, ocular surface disease index (OSDI), the tear film and optical coherence tomography were observed at 2, 4, 6, and 8wk before and after treatment. RESULTS: The best corrected visual acuity (BCVA, logMAR) was improved to 0.22 and 0.27 after treatment from baseline of 0.35 and 0.36 in groups A and B (P<0.05), respectively. After 8wk treatment, the central subfield thickness (CST), and subretinal fluid volumn (SFV) decreased significantly to 49.5% and 78.8% in group A and 37.0% and 57.2% in group B. There were significant differences of CST and SFV in both groups (all P<0.05). CONCLUSION: Fenofibrate combined with spironolactone may have more clinical efficacy in the treatment of CSCR than fenofibrate only.