Background: Eculizumab (ECU) a complement component 5 (C5) inhibitor, is the current standard of care for patients with paroxysmal nocturnal hemoglobinuria (PNH). Ravulizumab (RAV) is engineered from ECU with the main advantage of having an extended 8-week (vs 2-week with ECU) dosing interval, which decreases treatment burden markedly. Hence, RAV is expected to become the new standard of care to treat PNH. In Switzerland, RAV was approved for PNH treatment in 2020. Aims: The objective of this study was to evaluate data from the PNH Swiss Soliris and Ultomiris Reimbursement Registry (SSURR) to assess key parameters for safety and effectiveness of ECU and to assess the adoption of RAV for PNH treatment by physicians under real-world conditions. Methods: The SSURR was designed in 2012 as a prospective, longitudinal, multi-center registry study in Switzerland. Patients were recruited and followed in 9 centers. Health-related data were collected at the first consultation (baseline) and during follow-up visits. In this report, results are based on data collected from 23 February 2012 to 30 September 2021. Data were summarized using descriptive analysis. Ethics approval was obtained. All participants provided written informed consent. Results: In total, 56 patients with a median age of 51 (range 20-84) years were enrolled in the Registry, 52% were female. For 42 patients, the 12-month follow-up (FU) was available: 39 patients on ECU and 3 on RAV (switched from ECU). Median FU was 27 (range 12-108) months. Hemoglobin (Hb) mean was 63 ± 47 g/L at baseline (n=41), and Hb mean was 105 ± 25 g/L (n=26) at the last visit. The lactate dehydrogenase (LDH) decreased from a mean 1457 ± 706 U/L (baseline, n=42) to 403 ± 212 U/L after 12 months FU (n=40; 65% of patients < 1.5 × upper limit of normal [ULN]), and was for 88% of the patients < 1.5 × ULN at their last visit (n=24). Thrombosis events (TE) were reported in 33% of patients prior to treatment start (n=42) and 3 (7%) had thrombosis during FU of which 2 patients had no prior history of TE. Within 12 months prior to treatment start, 21 patients (50%) received one or more red blood cell (RBC) transfusions. At 12 months of FU, 91% (n=42) were RBC transfusion-free. RBC transfusions remained reduced (82%; n=27 at last visit). After 12 months FU, 19% (n=8) of the patients had withdrawn from the registry due to allogenic bone marrow transplantation, low PNH clone size, transformation to hypoplastic MDS, and 5 non-disease related reasons. Eight patients from the 56 enrolled received RAV as initial treatment. They were all C5-inhibitor treatment-naïve with a mean LDH level of 1481 ± 1432 U/L at inclusion, which decreased to 230 ± 62 U/L at the 6-month visit (n=4; all below 1.5 × ULN). Of the 56 enrolled patients with PNH, 43% were switched from ECU to RAV. These patients (58% female) had a median age of 55 (range 26-85) years and 75% of them had LDH < 1.5 × ULN at their last LDH measurement on ECU before RAV administration. There were 7 patients with a 6-month FU after switching at which 6 of them had a LDH below 1.5 × ULN. Summary/Conclusion: The current analysis provides real world evidence for the safety and effectiveness of ECU in the Swiss PNH patient population, demonstrated by pronounced reduction in LDH, low need for RBC transfusion and stable hemoglobin as well as reduced occurrence of thrombosis. The fast adoption of RAV demonstrates RAV may likely become the new standard of care for patients with PNH. In time, more data will become available for safety and effectiveness of RAV under real-world conditions.