OBJECTIVE: To identify clinical and environmental factors associated with an outbreak of hospital-onset, healthcare facility-associated Clostridium difficile infection (HO-HCFA CDI). DESIGN: Case-control study. SETTING: Public, acute care, academic tertiary referral center in Mexico. PATIENTS: Adults hospitalized ≥48 hours between January 2015 and December 2016 were included. Cases were patients with a first episode of HO-HCFA CDI. Controls were patients with any other diagnosis; they were randomly selected from the hospital discharge database and matched in a 1:2 manner according to the date of diagnosis of case ± 10 days. Variables with p