Lead extraction (LE) is necessary for patients who are suffering from a related infection, or in opening venous occlusions that prevent the insertion of additional lead. In severe cases of fibrous encapsulation of the lead within a vein, laser-based cardiac LE has become one of the foremost methods of removal. In cases where the laser radiation (typically at 308 nm wavelength) interacts with the vein wall rather than with the fibrotic lesion, severe injury and subsequent bleeding may occur. Selective tissue ablation was previously demonstrated by a laser operating in the UV regime; however, it requires the use of sensitizers (e.g.: tetracycline). In this study, we present a preliminary examination of efficacy and safety aspects in the use of a nanosecond-pulsed solid-state laser radiation, at 355 nm wavelength, guided in a catheter consisting of optical fibers, in LE. Specifically, we demonstrate a correlation between the tissue elasticity and the catheter advancement rate, in ex-vivo experiments. Our results indicate a selectivity property for specific parameters of the laser radiation and catheter design. The selectivity is attributed to differences in the mechanical properties of the fibrotic tissue and a normal vein wall, leading to a different photomechanical response of the tissue’s extracellular matrix. Furthermore, we performed successful in-vivo animal trials, providing a basic proof of concept for using the suggested scheme in LE. Selective operation using a 355 nm laser may reduce the risk of blood vessel perforation as well as the incidence of major adverse events.