Clostridium difficile is the most common pathogen between health care-associated infections and its incidence has increased during the last years. lack of enough evidence about effective hygiene interventions to prevent this disease. Due to the coronavirus disease 2019 (COVID19) pandemic, several strategies to reduce microorganism spread were adopted in hospital setting. The objective of this study was to establish whether such strategies can reduce health care associated C difficile infection (HA-CDI) incidence. We found that, during the pandemic (2020) HA-CDI incidence was significantly lower with respect to the previous years. This work demonstrates that maintaining this level of attention regarding control activities related to prevention of microorganism transmission significantly reduce HA-CDI and related expenses in terms of health costs and human lives.