PURPOSE: To compare the efficacy and safety of half-fluence vs half-dose photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSC). DESIGN: Multicenter retrospective comparison study. METHODS: Retrospective review of 56 patients affected by chronic CSC, including 28 patients (31 eyes) who received half-fluence PDT and 28 patients (29 eyes) who received half-dose PDT. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), and resolution of subretinal fluid on optical coherence tomography at 1 and 12 months were assessed. RESULTS: The mean logMAR BCVA improved significantly (P < .001), both in the half-fluence group (from 0.187 [± 0.187] to 0.083 [± 0.164]) and in the half-dose group (from 0.126 [± 0.091] to 0.068 [± 0.091]), at 12 months, without significant difference between the 2 groups. At 1 month a complete resolution of subretinal fluid was observed in 19 half-fluence-treated eyes (61.3%) and in 25 half-dose-treated eyes (86.2%) (P = .04). At 12 months, a complete resolution of subretinal fluid was achieved in 26 half-fluence-treated eyes (83.9%) and 29 half-dose-treated eyes (100%) (P = .0529). Nine eyes (29%) in the half-fluence group and 5 eyes (17.2%) in the half-dose group had at least 1 recurrence of subretinal fluid during the follow-up. Overall there were 15 and 5 recurrences in the half-fluence PDT and half-dose PDT groups, respectively (P = .07). In no eye of either groups was atrophy of the retinal pigment epithelium observed in the area of treatment. CONCLUSION: Half-dose PDT induced a more rapid reabsorption of the fluid, a more lasting effect, and equal safety with respect to half-fluence PDT.