The type of central vascular access device providers chosen for providing parenteral supportive treatments has evolved over the past years, going from routinely used centrally inserted catheters to a more recent trend of peripherally‐inserted central catheters (PICCs) when expected treatment duration is less than 6 months. This multicenter retrospective study aimed to provide a comprehensive assessment of the safety of PICCs in administering parenteral supportive treatments. All adult inpatients and outpatients who had a PICC inserted for the administration of parenteral supportive treatments (i.e., parenteral nutrition, intravenous fluids, blood products, or antibiotics) between September 2007 and December 2014 in four public Italian hospitals were included. The primary outcome was PICC removal because of an adverse event (AE, defined as occlusion, exit‐site infection, or symptomatic thrombosis). Among the 1,250 included patients, 178 PICC‐related removals because of AEs (14.2%; 1.62 AEs per 1,000 PICC days) were reported. Rates of PICC removal because of occlusion, exit‐site infection, and symptomatic thrombosis were 1.08, 0.32, and 0.23 per 1,000 PICC days, respectively. The median dwell‐time between PICC insertion and its removal because of an AE was 67 days (interquartile range 28–180 days). Risk of PICC removal due to AE was higher with open‐system PICCs [hazard ratio = 2.75, 95% confidence interval 1.52–4.96]. In this study, we found preliminary evidence that PICCs can be safely used to administer parenteral supportive treatments lasting up to 6 months. PICCs may be a relevant alternative to centrally inserted catheters for medium‐term parenteral supportive treatments.