PURPOSE: To evaluate the outcome of a prospective protocol for the treatment of chronic central serous chorioretinopathy (CSC). METHODS: Interventional prospective case series in 59 eyes (59 patients) with active chronic CSC. All patients were first treated with indocyanine green angiography (ICGA)-guided half-dose photodynamic therapy (PDT). In case of persistent serous subretinal fluid (SRF) after a follow-up period of at least 6 weeks, ICGA-guided PDT was repeated. If the SRF persisted after two PDT treatments, additional ICGA-guided high-density subthreshold diode micropulse laser (HSML) therapy was performed. Clinical evaluation included best-corrected visual acuity (BCVA), fundoscopy, OCT, fundus autofluorescence, fluorescein angiography and ICGA. RESULTS: After a single PDT treatment, complete resolution of SRF was seen in 37 of 59 eyes. Of the 22 eyes with no complete resolution of SRF, 19 eyes received a second PDT treatment, after which seven eyes of the 19 eyes showed a complete resolution of SRF. Ten eyes underwent HSML, of which one eye had complete resolution of SRF within 7 weeks. At final follow-up a complete resolution of SRF was present in 80% of all eyes. The mean BCVA improved from 0.28 logMAR at baseline to 0.16 logMAR at final follow-up. Improvement of BCVA was highest after the first treatment (-0.12 logMAR, p < 0.001). CONCLUSIONS: The proposed treatment strategy using half-dose PDT and HSML in active chronic CSC resulted in an anatomical success rate of 80%. The first half-dose PDT treatment has the highest likelihood of a favourable treatment response on OCT and BCVA increase.