With the worldwide spread of SARS-CoV-2 disease, people with cystic fibrosis (CF), especially solid organ transplant recipients, have quickly been identified as a risk group for severe disease. Studies have shown low antibody response to SARS-CoV-2 vaccines in recipients of solid organ transplant compared to the healthy population. Information on immune response in CF patients with solid organ transplantation is limited, especially regarding long-term efficacy. The aim of this real-world study was a long-term assessment of humoral immune response induced by three and four doses of the SARS-CoV-2 mRNA vaccine. S1RBD and IgG antibodies were measured every 12 weeks over a period of 27 months in twelve CF patients (five liver and seven lung transplantation recipients). A total of 83.3% of our patients showed a positive antibody response after three doses of the SARS-CoV-2 mRNA vaccine. A sustained immune response was observed in both groups over the observation period, with liver transplant recipients showing higher levels than lung transplant recipients. This study is among the first to show long-term data with constantly elevated or even increasing antibody levels. We conclude that this effect is most likely associated with repeated boostering in terms of infections and booster vaccinations.