To compare the progression rate of primary with secondary chronic venous disease (CVD). Patients with a first episode of proximal deep vein thrombosis (DVT), diagnosed by duplex ultrasound (DU) were included in group A - secondary CVD (41 patients, 46 limbs). DU was performed at least once, 1 year after the diagnosis, and repeated at 5 years. Group B - primary CVD (41 patients, 50 limbs) included age- and sex-matched patients with primary CVD and duration of 5 to 10 years to be comparable with that of group A. They had no history of DVT and were referred for reflux evaluation. All their veins were free of postthrombotic signs upon DU examination. Group C (15 patients, 30 limbs) had no signs and symptoms of CVD and were examined at baseline and 5 years later. This group of patients was also matched for age and sex. Clinic examinations were performed at 3, 6, and 12 months and yearly thereafter. The CEAP system was used to grade disease severity. The proximal veins were divided in the CFV, FV, and POPV segments for analysis. Thrombosed veins were subsequently graded as complete, partial, and fully recanalized. Recurrent DVT cases were also recorded. At 5-year follow-up, the prevalence of skin damage was significantly higher in group A (11/46 vs group B 3/50, P = .019 and vs group C 0/30, P < .01). The progression to skin damage in group A was faster as it changed from 4% (2/46) at 1 year (P = 0.014) compared with the two other groups. In group A, 22 limbs had reflux, three had obstruction, 19 had combine reflux and obstruction, and two were normal. In group B, superficial, deep, and perforator vein reflux were seen in 50, 4, and 15 limbs, respectively. In group C, five limbs in four patients developed superficial reflux in which only two had symptoms. The CEAP class in this group was C0N = 25, C1 = 3, and C2 = 2. In group A, skin damage was significantly higher in limbs with combined proximal and distal obstruction as well as in limbs with combined reflux and obstruction (P = .012 and P = 0.013, respectively). DVT was found in 108 segments (25 CFV, 40 FV, and in 43 POPV), 82 at the first episode and 26 as an ipsilateral recurrence. Ipsilateral and contralateral recurrences were seen in 21.9% and 9.8% of patients, respectively. Complete recanalization occurred in 43 segments, partial in 55, and none in 10. Reflux occurred in 85.5% and 60.5% of the partially and completely recanalized segments, respectively (P = .006). The progression of CVD is more rapid in postthrombotic limbs when compared with those with primary CVD. The incidence of CVD in normal individuals is small and its progression is slow. Poor prognostic factors for progression to advanced CVD include the combination of reflux and obstruction, ipsilateral recurrent DVT, and multi-segmental involvement.