Deep Venous Thrombosis (DVT) due to Peripherally Inserted Central Catheter (PICC) is one of the most threatening complications after device insertion. To assess the rate of PICC-associated DVT and analyze the risk factors associated with this event in cancer and critically ill patients. We conducted a descriptive, retrospective cohort study with 11,588 PICCs from December 2014 to December 2019. Patients ≥ 18 years receiving a PICC were included. Pre-and post-puncture variables were collected and a logistic regression was used to identify the independent factors associated with the risk of DVT. The DVT prevalence was 1.8% (n = 213). The median length of PICC use was 15.3 days. The median age was 75 years (18; 107) and 52% were men, 53.5% were critically ill and 29.1% oncological patients. The most common indications for PICC's were intravenous antibiotics (79.1%). Notably, 91.5% of PICC showed a catheter-to-vein ratio of no more than 33%. The tip location method with intracavitary electrocardiogram was used in 43%. Most catheters (67.9%) were electively removed at the end of intravenous therapy. After adjusting for cancer profile ou chemotherapy, regression anaysis revealed that age (OR 1.011; 95% CI 1.002-1.020), previous DVT (OR 1.96; 95% CI 1.12-3.44) and obstruction of the device (OR 1.60; 95% CI 1.05-2.42) were independent factors associated with PICC-associated DVT, whereas the use of an anticoagulant regimen was a protective variable (OR 0.73; 95% CI 0.54-0.99). PICC is a safe and suitable intravenous device for medium and long-term therapy, with low rates of DVT even in a cohort of critically ill and cancer patients.