BACKGROUND There are few reports on total parenteral nutrition (TPN) and its possible prothrombotic effect. The purpose of this study was to identify risk factors for subclavian vein thrombosis (SVT) in patients receiving TPN. METHODS Cancer patients with indwelling subclavian catheters and TPN were followed in a cohort study. Doppler ultrasound examination was performed 8 and 30 days after catheter placement. RESULTS One hundred twenty-one patients were included, with a mean of 61 (± 11.8) years of age. We detected 36 SVT events at day 8 (29.8%) and 47 (38.8%) at day 30 after central catheter placement. Mean length of subclavian catheterization was 17.2 (± 8.2) days. Fifty-three point three percent of patients receiving ≥ 3,050 mOsm TPN in 24 hours developed SVT (relative risk (RR) = 2.01, 95% CI, 1.14 - 3.57; P = 0.016) at day 8 and 60% (RR = 1.67, 95% CI, 1.30 - 2.71; P = 0.038) at day 30 post-catheter placement. Protein administration of > 97.5 g/day was shown to be a risk factor for early thrombosis with a mean of 16.88 days for the development of SVT (95% CI, 10 - 23.7) versus 27.8 days (95% CI, 25.8 - 29.9) in the group with nutritional protein content < 97.5 g/day (P = 0.000). CONCLUSIONS High-osmolarity and high-protein nutrition formulas were shown to be risk factors for SVT in cancer patients receiving TPN.