A stent-graft or prosthesis (10) with enhanced flexibility, in particular enhanced bending flexibility, includes a radially distensible stent (24) and at least one continuously uninterrupted ePTFE tubular graft or covering (18) having a node and fibril structure. The tubular stent (24) includes opposed open ends (12', 14') and a stent wall structure (26) having opposed exterior (28) and luminal surfaces (30). The ePTFE covering (18) is securably disposed to at least one of the stent surfaces (28, 30). The ePTFE graft or covering (18) includes a tubular wall (16) that is continuously uninterrupted and desirably substantially free of slits, apertures and folds. The ePTFE graft (18) further includes a first region (20) and a second region (22), where the first region (20) has a different bending flexibility from the second region (22).