Therapeutic ultrasound angioplasty is an emerging minimally invasive cardiovascular procedure for disrupting atherosclerotic lesions using small diameter wire waveguides. The lesions are damaged through a combination of direct ablation, pressure waves, cavitation and acoustic streaming caused by distal-tip displacements at ultrasonic frequencies. Numerical and experimental methods are used to investigate the outputs of the wire waveguides during ultrasonic activation. A commercially available generator and acoustic horn are used in combination with Nickel-Titanium (NiTi) wire waveguides in this study. A laser sensor is used to measure the frequency and amplitude output of the distal tip of the wire waveguide, and this is compared to amplitude estimations obtained using an optical microscope. Power is observed to affect both amplitude and frequency. Clinical devices will require long, flexible waveguides with diameters small enough to access the coronary arteries. A finite element model is used to design tapered sections in long wire waveguides in order to achieve low profile distal geometry, and improve ultrasonic wave transmission. These tapered sections reduce the wire waveguide diameter in two stages, firstly from 1 to 0.35mm and then from 0.35 to 0.2, while increasing the amplitude of the ultrasonic wave by factors of 2.85 and 1.75, respectively. The numerical model also showed damping could potentially be a significant problem in long untapered wire waveguides (>l.5m). Experimental ablation trials were conducted using the tapered long wire waveguides, including assessment of the effect of various combinations of bend radii and bend angles. The waveguide was found to perform well, but increased power levels were required to transmit ultrasound through tortuous waveguide configurations.