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Background real-world data on COVID-19 vaccine safety, immunogenicity and acceptance in adults with congenital heart disease (ACHD) are lacking. Methods ACHD patients who were offered COVID-19 vaccination from January to June 2021 were included. Data on adverse events, on patients’ attitude towards vaccination and antispike IgG titre were retrospectively collected. A group of healthy individuals with similar age and sex undergoing vaccination was included for comparison. Results 208 patients followed in a single ACHD tertiary centre (33.3 [26–45]years,54%male) received COVID-19 vaccine, 65% vaccinated at our institution: 199 (96%)received Pfizer–BioNTech BNT162b2 vaccine, 4 (2%)Moderna-1273 and 5 (2%)AstraZeneca–ChAdOx1. Median follow-up after vaccination was 79 [57–96]days. No major adverse event was reported and there was no difference in the in adverse events incidence between ACHD patients and the control group. One patient was diagnosed with acute pericarditis. There were two unrelated deaths during follow-up. Three (1.5%)vaccinated patients tested positive for COVID-19. Antispike IgG titre, available in 159 (76%)patients, was 1334 [600–3401]BAU/ml, not significantly different from the control group (p = 0.2). One patient with Fontan failure was seronegative. Advanced physiological stage was related to lower antibody response, independently from previous viral exposure (p, Graphical abstract Image 1