Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections and an important cause of morbidity and mortality worldwide. The objective of the study was to identify the predictive factors for unfavorable evolution and deaths among patients with CDI. Materials and methods: We conducted a retrospective, observational, non-randomized study on 202 patients diagnosed with CDI in the Clinical Emergency Hospital of Bucharest, Romania, for a period of two years. For the statistical analysis, the R program was used, with p-values <0.05 being considered statistically significant. Results: The average age of the patients included in the study was 70.8 years, the average duration of hospitalization was 18.4 days, and the mortality rate was 25.7%. During the follow-up period, only 5% of the patients presented a recurrence of CDI. Multiple binomial logistic regression defined as independent risk factors for death among CDI patients: advanced age, comorbidities such as chronic obstructive pulmonary disease (p=0.008), chronic kidney disease (p=0.007), or COVID-19 (p=0.036), leukocytes ≥ 16,755/mm3 (p=0.009) and serum albumin < 2.83 g/dL (p<0.001). Conclusions: The identification of certain negative prognostic factors in patients with CDI requires a careful follow-up of the patients, for an early identification of complications and adaptation of therapeutic management.