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BACKGROUND AND OBJECTIVES This study aimed to compare the efficacy of fluorescein angiography (FA)-guided and indocyanine green angiography (ICGA)-guided half-time photodynamic therapy (PDT) for central serous chorioretinopathy (CSC). SUBJECTS AND METHODS Medical records of 61 eyes of 61 CSC patients who underwent half-time PDT were retrospectively reviewed. The irradiation area was determined using information from FA or ICGA with physicians' discretion. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SCT), and resolution of subretinal fluid (SRF) were evaluated at baseline and 1, 3, 6, and 12 months after PDT. RESULTS A total of 29 and 32 eyes received FA-guided PDT (irradiation area, 2898.3 ± 705.7 μm) and ICGA-guided PDT (irradiation area, 4993.8 ± 333.1 μm), respectively. A significant improvement in the mean BCVA was found at 1 month in the FA-guided group (P = 0.02), but not in the ICGA-guided group (P = 0.88). BCVA was significantly improved in both groups at 3, 6, and 12 months with no significant intergroup difference at any time points. CRT and SCT were significantly reduced in both groups at all time points with no significant intergroup differences. No significant intergroup differences were observed in the rate of recurrence and persistent SRF. However, there was a significant difference between groups in the rate of recurrence and/or persistent SRF (P = 0.04). Multivariate analysis revealed that choice of FA-guided was significantly associated with recurrence and/or persistent SRF (P = 0.04). CONCLUSION Half-time PDT with ICGA-guided irradiation spot might be more effective than that with FA-guided in treating CSC patients in complete resolution of SRF.