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Summary. Background: The aim of this study was to investigate whether inflammatory markers (interleukin-6 [IL-6] and C-reactive protein [CRP]) in the acute phase of deep vein thrombosis (DVT) are associated with elevated venous outflow resistance (VOR), thrombosis score (TS), reflux and the development of clinical post-thrombotic syndrome (PTS). Methods: In 110 patients with a first DVT, plasma concentrations of IL-6 and CRP were determined on the day of admission. VOR, TS and reflux were measured 7 days, 1 and 3 months after diagnosis. After 1 year patients were evaluated for PTS using the Clinical, Etiologic, Anatomic and Pathophysiologic (CEAP) classification and Villalta scale. Results: Median levels of IL-6 and CRP were 7 pg mL−1 and 21 mg L−1, respectively. After 3 months, VOR was elevated in 33 patients (30%), TS in 33 (30%) and reflux in 57 (52%). Incidence of PTS was 36.7% using CEAP ≥ 3 and 35.4% using Villalta-scale ≥ 5. Elevated levels of IL-6 and CRP were related to higher outcomes of VOR after 3 months [relative risks (RR) 2.4 (95% CI 1.5–3.9) and 1.4 (1.1–3.3), respectively] and for IL-6 to TS [1.5 (1.1–2.1)]. For reflux no relation was found. After 90 days, elevated outcomes of VOR, TS and reflux were related to PTS after 1 year. The association of IL-6 and CRP with PTS was weak using the CEAP classification with a RR of 1.2 (0.7–2.2) and 1.8 (0.9–3.3) and absent according to the Villalta scale 0.6 (0.2–1.4) and 1.2 (0.6–2.5), respectively. Conclusion: The results of this study suggest that inflammation might play a role in incomplete thrombus clearance, venous outflow obstruction and the development of PTS after 1 year.