Hospital-Onset COVID-19 Infection (HOCI) encloses still a major risk of transmission and morbimortality, threatening regular activity. The aim of this study is to compare the dynamics of transmission of HOCI of patients attended along the pandemic. This observational longitudinal study included all COVID-19 cases identified, by polymerase chain reaction or rapid antigen tests, in a large tertiary hospital in Barcelona, Spain, between February 25, 2020 and March 25, 2022. HOCI cases were diagnosed either by symptoms or weekly screening during admission, and therefore isolated. Cases and their in-hospital contacts were followed-up. Six periods were defined according to Barcelona’s COVID-19 incidence waves. Serial intervals and secondary attack rates (SAR) were calculated, comparing SARs by incidence rate ratios (IRR) between periods and by other clinical and epidemiological factors, using negative binomial regression. From the 11,752 COVID-19 cases attended, 531 (4.5%) were HOCI cases, which fluctuate with community incidence. Morbimortality decreases along time (18% and 11.4% reduction in ICU admission and deaths rates, respectively). Contacts (n=1976) were identified in rooms (12.9%) and other settings. Series interval reduces, from a median (IQR) of 4.0 (1.5-6.5) to 3.0 (1.5-4.5) days in the last period. Global SAR is 11.0 cases/100 contacts, reaching 26.8 cases/100 contacts when sharing room, the main factor affecting SAR (IRR 1.8; 95%CI 1.5-2.3). Vaccination did not significantly influence transmission (IRR 0.8; 95%CI 0.7-1.0). SAR peaks in the third period (37.5 cases/100 contacts), resurging in the last period (21.4 cases/100 contacts). HOCI’s SAR remains high, specially in shared rooms. Transmission becomes faster, as new variants spread (e.g. omicron). Vaccination impact on transmission is low-moderated in COVID, as in other respiratory infections (e.g. influenza). Thus, surveillance in vulnerable hospital population remains key for rapid identification, early treatment, prevention of new cases and avoiding services collapse in high incidence periods, as winter.