Abstract Background Peripherally inserted central venous catheters (PICCs) serve as an alternative to short-term central venous catheters (CVCs) for providing intravenous access in hospitalized patients. Although a number of studies suggest that PICCs are associated with a lower risk of central line-associated bloodstream infections (CLABSIs) than CVCs, recent data concerning specific patient groups support the contrary. In this regard, we are comparing CVC- and PICC-related CLABSI rates developed in a selected group of critically ill inpatients and evaluating the CLABSI microbiological distribution. Methods The study was conducted at a tertiary care hospital in Greece between May 2017 and May 2019. We performed a two-year retrospective analysis of the data collected from medical records of consecutive adult patients who underwent PICC or CVC placement. Results A total of 1187 CVCs placed for 9774 catheter-days and 639 PICCs placed for 11,110 catheter-days, were reported and analyzed during the study period. Among CVCs, a total of 59 (4.9%) CLABSIs were identified, while among PICCs, 18 (2.8%) cases presented CLABSI (p = 0.029). The CLABSI incidence rate per 1,000 catheter-days was 6.03 for CVC group and 1.62 for PICC group (p