The efficacy of local drug delivery in the treatment of coronary artery disease is limited by the relatively low delivery efficiency of the available devices. A unique local drug delivery device, the Infiltrator catheter (InterVentional Technologies, Inc.), has been designed specifically to enhance efficiency by injecting drugs directly into the arterial wall through microports mounted on the balloon surface. The purpose of this study was to assess the efficiency of delivery of this device in the porcine coronary model and to compare it to a previously validated device, the hydrogel balloon (Boston Scientific, Maple Grove, Minnesota). Studies were also performed to assess the pattern of intramural heparin deposition following delivery with the Infiltrator catheter and to assess the effect of the microports on vascular integrity. The efficiency of delivery was significantly greater with the Infiltrator catheter than with the hydrogel balloon (4.5% vs. 0.08%; p = 0.02). Similarly, the absolute amount of intramurally deposited heparin was greater with the Infiltrator (111.3 +/- 38.5 units vs. 2.4 +/- 0.85 units; p = 0.02) despite the fact that more heparin was delivered with the hydrogel catheter. Histologic studies revealed characteristic discrete puncture channels in the vessel wall due to penetration of the microports. Other than this histologic finding, there was no significant difference in the extent of architectural disruption between the Infiltrator and conventional balloon inflations. Fluorescein-labeled heparin studies revealed heparin to be diffusely distributed throughout the vessel wall immediately following delivery with the Infiltrator. We conclude that the Infiltrator catheterOs unique mechanism of delivery improves the efficiency of local drug delivery without excessive vessel wall trauma.