OBJECTIVES: This study aimed to analyze the prevalence of long-term central line-associated bloodstream infections (CLABSI) among hospitalized adults with cancer in Italy and compare the characteristics of patients who required long-term central venous access device (LCVAD) substitution due to prior CLABSI with those who had never experienced CLABSI. METHODS: The study was conducted in hospitals across northern and central Italy using a multicenter, observational, cross-sectional design from March to September 2021. A total of 174 adults with cancer were included. Data were collected through electronic case report forms, including demographic, clinical, treatment-related, and catheter-related variables. Propensity score matching (PSM) was used to compare the characteristics of patients who underwent LCVAD substitution due to previous CLABSI with those who never experienced CLABSI. Multiple correspondence analysis (MCA) was conducted to explore the patterns within matched subgroups. RESULTS: The prevalence of CLABSI was 3 %, and 5.2 % of patients required LCVAD substitution due to prior CLABSI. After applying PSM, the groups were successfully balanced for sex, age, presence of metastases, comorbidities, BMI, received treatments, corticosteroid therapy, ongoing antibiotics, hormone therapy, type of LCVAD, lumens, and utilization frequency. Hematologic cancer was more frequent in the CLABSI group (44.4 %) compared to the non-infective group (0), with a statistically significant difference (P = 0.045). MCA revealed potential patterns among matched subgroups but did not identify statistically significant associations: patients with previous LCVAD substitution were more frequently associated with a history of prior infections, ongoing antibiotic therapy, and unspecified primary lesion locations; conversely, patients who never experienced CLABSI tended to cluster around characteristics such as hormone therapy and corticosteroid therapy. CONCLUSIONS: These findings emphasize the importance of continuous monitoring, individualized infection prevention strategies in oncology nursing practice. Future research with larger datasets is needed to validate these findings and develop tailored interventions to reduce CLABSI risks.