Apparatus and methods provide distal protection while accessing blood vessels within a patient's vasculature. A flexible sheath and distal protection element, e.g., a balloon or filter, are carried by a stiffening member. The sheath is lubricious and has a relatively thin wall, thereby providing a collapsible/expandable guide for delivering fluids and/or instruments. The sheath is advanced into a blood vessel in a contracted condition, expanded to an enlarged condition to define a lumen, and the distal protection element is deployed within the vessel beyond the sheath. Fluids and/or instruments are introduced into the vessel via the sheath lumen, the distal protection element retaining the fluids and/or capturing emboli released by the instruments. Upon completing the procedure, the sheath, distal protection element, and stiffening member are removed from the vessel.