As in previous surveys, the 2022 National Prevalence Survey (NPS) aims to measure and describe the national prevalence of healthcare-associated infections and antimicrobial treatments in healthcare facilities. With 1,155 participating healthcare facilities (a participation rate of 42.5%), 151,676 patients were included in the 2022 ENP. The prevalence of infected patients in 2022 (5.71% 95% CI [5.45–5.99]) increased compared to that measured in 2017 (4.98% 95% CI [4.62–5.36]). This increase is notably linked to the inclusion of nosocomial COVID-19 cases in the 2022 ENP, which accounted for half of the increase in the prevalence of infected patients between 2017 and 2022. After excluding nosocomial COVID-19 cases, the prevalence of infected patients in 2022 still increased (+7.5%) but not significantly compared to the 2017 estimate. Overall, the increase in the prevalence of infected patients was observed among patients with at least one risk factor for infection (being 65 years of age or older, having undergone surgery since admission, having a condition with a 1- or 5-year life-threatening prognosis, being immunocompromised, having a malignant condition) and among patients without any risk factors for infection. The prevalence of patients treated with systemic antibiotics in 2022 (16.24% 95% CI [15.66–16.84]) increased compared to 2017 (15.12% 95% CI [14.22–16.06]). This trend is observed across all age groups, genders, and patient health statuses. These results underscore the need to continue efforts to prevent healthcare-associated infections by targeting the most common infections (urinary tract infections, pneumonia, surgical site infections, bacteremia) and to strengthen initiatives promoting the appropriate use of antibiotics.