BackgroundAdjunctive catheter-directed thrombolysis (CDT) shows variable efficacy in preventing postthrombotic syndrome (PTS), despite restored patency. ObjectivesThis CAVA-trial subanalysis investigated the effect of ultrasound accelerated (UA)CDT on patency, reflux and their relevance in PTS development. MethodsThis multicentre, randomised, single-blind trial, enrolled patients (18-85 years), with a first iliofemoral deep vein thrombosis (DVT) and symptom duration ≤14 days. Patency and reflux were assessed by duplex ultrasound (DUS) at 12 months (T12) and long-term (LT) follow-up (median 39.5 (24.0-63.0) months). PTS was diagnosed using the Villalta score. ResultsUACDT significantly improved patency in all vein segments at T12 (60.3% UACDT vs. 25.9% standard treatment (ST), p=0.002) and LT (45.2% UACDT vs. 11.9% ST, p<0.001). Popliteal patency, however, was similar between groups (87.9% UACDT vs. 83.3% ST, p=0.487). Reflux was similar between groups at T12 and LT, only popliteal reflux was significantly reduced in the UACDT group at LT (22.6% UACDT vs. 44.8% ST, p=0.010). Absent iliac patency at T12 was associated with increased PTS risk in the ST-group only (OR 10.84 [1.93-60.78]; p=0.007). In the UACDT group popliteal reflux at T12 was associated with moderate-severe PTS at T12 (OR 4.88 [1.10-21.57]; p=0.041) and LT (OR 5.83 [1.44-23.63]; p=0009). Combined popliteal reflux and absent iliac patency significantly amplified PTS risk (OR 10.79 [2.41-48.42]; p<0.001). ConclusionUACDT improves patency and reduced popliteal reflux. Iliac patency and popliteal reflux are independently associated with moderate-severe PTS and contribute synergistically to its development. However, a proportion of moderate-severe PTS cases lacks an evident underlying cause.