BACKGROUND: In healthcare facilities, nosocomial transmissions of respiratory viruses are a major issue. SARS-CoV-2 is not exempt from nosocomial transmission. Our goals were to describe COVID-19 nosocomial cases during the first pandemic wave among patients in a French university hospital and compliance with hygiene measures. METHODS: We conducted a prospective observational study in Grenoble Alpes University Hospital from 01/03/2020 to 11/05/2020. We included all hospitalised patients with a documented SARS-CoV-2 diagnosis. Nosocomial case was defined by a delay of 5 days between hospitalisation and first symptoms. Hygiene measures were evaluated between 11/05/2020 and 22/05/2020. Lockdown measures were effective in France on 17/03/2020 and ended on 11/05/2020. Systematic wearing of mask was mandatory for all healthcare workers (HCW) and visits were prohibited in our institution from 13/03/2021 and for the duration of the lockdown period. RESULTS: Among 259 patients included, 14 (5.4%) were considered as nosocomial COVID-19. Median time before symptom onset was 25 days (interquartile range: 12-42). Eleven patients (79%) had risk factors for severe COVID-19. Five died (36%) including 4 deaths attributable to COVID-19. Two clusters were identified. The first cluster had 5 cases including 3 nosocomial acquisitions and no tested HCWs were positive. The second cluster had 3 cases including 2 nosocomial cases and 4 HCWs were positive. Surgical mask wearing and hand hygiene compliance were adequate for 95% and 61% of HCWs, respectively. CONCLUSIONS: The number of nosocomial COVID-19 cases in our hospital was low. Compliance regarding mask wearing, hand hygiene and lockdown measures drastically reduced transmission of the virus. Monitoring of nosocomial COVID-19 cases during the first wave enabled us to determine to what extent the hygiene measures taken were effective and patients protected. Trial registration Study ethics approval was obtained retrospectively on 30 September 2020 (CECIC Rhone-Alpes-Auvergne, Clermont-Ferrand, IRB 5891).