Increased plaque vascularization is causatively associated with the progression of unstable atherosclerotic vessel disease. We investigated the safety and efficacy of heat-generating radiofrequency ablation (RFA) in reducing the number of vessels in the plaque and adventitia and its effect on plaque size and composition. To this end, New Zealand White rabbits were fed a cholesterol-enriched diet and subjected to balloon denudation of the infrarenal aorta to induce atherosclerotic plaque formation. After 13 weeks, the proximal or distal half of the infrarenal aorta was exposed to transluminal RFA. The untreated half served as an intra-individual control. Optical coherence tomography (OCT) was performed directly after RFA. We found that RFA on the rabbit atherosclerotic plaque is safe and leads to decreased intraplaque vessel density and smooth muscle cell content but does not affect other components of plaque composition or size.