A catheter and methods for luminal therapy are provided wherein a catheter has an outer balloon with a multiplicity of apertures for infusing one or more therapeutic agents into a vessel wall, an intermediate balloon having a multiplicity of apertures offset from the apertures of outer balloon to serve as a baffle that reduces jetting and promotes uniform distribution of therapeutic agent exiting through the outer balloon, and an impermeable inner balloon disposed within the intermediate balloon that enables the intermediate and outer balloons to be forced into engagement with the vessel wall to dilate the vessel and disrupt plaque lining the vessel wall and to also facilitate the uniform delivery of the therapeutic agent. The outer balloon may include protrusions that contact the vessel wall to disrupt the plaque, bumpers to reduce washout during infusion of therapeutic agents; the intermediate balloon may include a texture, ribs or protrusions on its outer surface to prevent adhesion to the outer balloon during dilation of the vessel; and the catheter may include a guide wire lumen sized to accept an energy delivery device to delivery energy that enhances uptake of the therapeutic agent or prolongs therapeutic effectiveness of the agent.