Central serous chorioretinopathy (CSCR) is an ocular disease characterized by serous detachment of the neurosensory retina at the posterior pole, with or without an associated retinal pigment epithelium (RPE) detachment. It is associated with different systemic diseases although the pathogenesis is unknown. Different therapies have been applied to treat CSCR with poor results. We reviewed the literature and found that in all the diseases associated with CSCR plasminogen activator inhibitor 1 (PAI-1) was increased. Acetyl salicylic acid (Aspirin) is effective in lowering PAI-1 levels and platelets aggregation; as such we decided to treat patients affected by CSCR with low dose Aspirin. From January 2005 to December 2008 we enrolled 107 patients, 85 male and 22 female, affected with active CSCR or the multifocal variant. Aspirin was administrated at an oral dose of 100 mg. per day for a month and then 100 mg. every other day for five months. After the first week of therapy and for the following three months the visual acuity improved and remained stable to the end of the follow-up (median follow-up 20 months). A recurrence of the disease interested the 6% of the patients. In this study low-dose Aspirin was able to treat central serous chorioretinopathy with a quick recovery of the visual acuity and a reduced number of recurrences during the follow-up. Besides the effectiveness of the treatment with Aspirin supports our observation regarding the role of impaired fibrinolysis and increased platelets aggregation in the choriocapillaris as genesis of CSCR.