Fibrinolytic therapies for arterial thrombosis can be limited by indadequate delivery of sufficient concentrations of drug. Thrombus vaporization with lasers creates vapor bubbles causing fluid displacement and pressure transients that may be a photoacoustic driving force to facilitate drug delivery. We studied the feasibility of using photoacoustic drug delivery (PADD) to deliver 1 μm fluorescent microspheres (MS) to 10 thrombosed porcine carotid arteries. A 1.0 mm laser ablated channel was created in each 5.0 mm diameter vessel with a single pass of a fluid core optical catheter (OC) - a 1 mm diameter teflon tube fitted with a 300 μm optical fiber coupled to a 2 μs pulsed dyle laser emitting 577 nm light at 50 mJ/pulse. Saline flowing through the OC carried light and MS to the thrombus. Treatment vessels (n=5) received PADD: laser energy and simultaneous delivery of MS solution (1x107/cc) at 4 cc/min via the OC. Control vessels (n=5) were infused with the MS solution for a similar time after the laser channel was created. Frozen sections were viewed under light and fluorescence microscopy. Areas and depth of MS penetration into thrombus were measured. An optical multichannel analyzer measured fluorescence intensity, normalized per MS. Laser pulses were equal (80±20 PADD vs. 86±7 control, p=NS). Mean MS penetration area and max depth of MS into thrombus were greater in PADD vessels (0.13±0.02 mm2 control, p=.01), (327±36 μm PADD vs 173±33 μm control, p=0.0002). We conclude that PADD can increase delivery of MS to arterial thrombi compared to infusion alone. PADD may be a means of faciltating thrombus removal through localized drug delivery.