Clostridioides difficile infections are the main cause of antibiotic-related diarrhea. Most of them come in the form of healthcare-associated Clostridioides difficile infections (HA-CDI). The aim of the study was to analyze HA-CDI epidemiology and the relationship between antibiotic consumption and CDI epidemiology at St Luke’s Provincial Hospital in Tarnow, Poland. In 2012–2018, surveillance of CDI was carried out in adult surgical wards at St Luke’s Provincial Hospital. The data were collected in accordance with the methodology of the Healthcare-Associated Infections Surveillance Network (HAI-Net), European Centre for Disease Prevention and Control (ECDC), and the ATC/DDD system (Anatomical Therapeutic Chemical Classification System) of the World Health Organization. In total, in the study period, 51 cases of CDI involved CA-CDI (24.5%) and 147 were HA-CDIs (75.5%). The most CA-CDIs were found in the general surgery (32.6%) and urology (17.0%) wards. CA-CDI incidence was 0.7/1000 patients and for HA-CDI it was 2/1000 patients (4.4/10,000 patientdays (pds)). The highest HA-CDI incidence was in the neurosurgical departments (18/10,000 pds) and oncological surgery (8.4/10,000) pds. There was a significant positive correlation between CA-CDI and HA-CDI (correlation of 0.943, p < 0.001) and between the number of patients hospitalized and HA-CDI (correlation of 0.865, p = 0.012). The total antibiotic consumption amounted to 0.7 DDD/10,000 pds; it was the highest in the urology ward (0.84/10,000 pds) and 49.5% of the antibiotics were fluoroquinolones (0.41/10,000 pds). On the basis of regression coefficients, a positive correlation was demonstrated between the use of fluoroquinolones and the HA-CDI incidence rate. Both a high percentage of CDI cases and a high intake of antibiotics were recorded in the urology department. About half of all antibiotics were fluoroquinolones.