Summary. Background: Post-thrombotic syndrome (PTS) occurs in 20-50% of patients after a deep venous thrombosis (DVT). It is difficult to accurately predict which patients will develop PTS. Biomarkers could be a valuable tool for PTS risk assessment. Objectives: To investigate whether increased levels of factor (F)VIII, C-reactive protein (CRP) or D-dimer, over time, are associated with the development of PTS in patients after an acute DVT. Methods: PTS status was assessed using the Villalta scale. Blood sampling was performed at three points during follow-up. Results: A cohort of 228 consecutive patients was included after an acute DVT. At T1 (12 months after index DVT), both levels of D-dimer (median 725 ng mL and independently associated with PTS. Persistent inflammation rather than hypercoagulability might be the most important etiological factor in PTS, and may be a target for future therapy. The development of a risk score for PTS, including both clinical risk factors and biomarker levels, such as CRP, might be desirable.