Purpose: The superficial femoral-popliteal vein (SFPV) is a reliable conduit for aortoiliac, infrainguinal, and venous reconstructions. In this prospective study, we characterized the anatomic and physiologic changes in SFPV harvest limbs and their relationship to the development of late venous complications. Methods: Since 1990, we have studied 61 patients after harvest of 86 SFPVs at 6-month intervals with clinical examinations, lower-extremity venous duplex, and venous function tests. The CEAP system was used as a means of categorizing clinical changes. Results: Mean (± SEM) follow-up was 37 ± 3 months. Less than one third of harvest limbs had edema without skin changes (C3). No patient had major chronic venous changes (C4 to C6) or venous claudication. There were no significant differences in limb measurements between harvest and non-harvest limbs, except in a subgroup of patients with unilateral harvest in which there was a small but significant (P = .046) increase in harvest limb thigh and calf circumference, compared with the opposite non-harvest limb. These clinical results were not affected by the presence or absence of an intact greater saphenous vein (GSV). Large, direct collaterals (4 to 6 mm in diameter) between the popliteal vein stump and profunda femoris vein (PFV) were seen by means of duplex ultrasonography in 29 harvest limbs (34%). The remainder appeared to have smaller, less direct collaterals to the PFV. Mild venous reflux with rapid cuff deflation was present at the popliteal or posterior tibial vein in nine of 79 harvest limbs (11%). Six of these nine limbs (67%) with reflux were clinical class C3, compared with only 19 of the 70 limbs without reflux (27%; P = .02). Ambulatory venous pressure (AVP) with exercise was significantly increased in harvest limbs (60 ± 4.7 mm Hg), compared with non-harvest limbs (47.8 ± 5.2 mm Hg; P = .049). The AVP recovery time of harvest limbs (14.0 ± 1.0 seconds) was reduced, compared with non-harvest limbs (23.5 ± 4.5 seconds; P = .02). AVPs (exercise) remained stable or decreased in six of 10 harvest limbs measured serially. Venous refill time in harvest limbs (15.1 ± 1.1 seconds) was shortened, compared with non-harvest limbs (22.3 ± 2.1 seconds)(P = .002). Venous outflow obstruction measured by means of plethysmography was present in 93% of harvest limbs, compared with 36% of non-harvest limbs (P = .001). Conclusion: SFPV harvest results in minimal mid-term to late-term lower-extremity venous morbidity despite outflow obstruction. The most likely mechanisms preserving clinical status include the low incidence of mild reflux, the presence of collateral venous channels, and the lack of progression in abnormal harvest limb physiology. The absence of the ipsilateral GSV does not adversely affect clinical outcome.