This work is a step towards the analysis of the effect of different laser applicator tips used for laser ablation of liver for in vivo experiments. As the thermal outcome of this minimally invasive treatment for tumors depends upon the interaction between the tissue and the light, the emission pattern of the laser applicator has a key role in the shape and size of the final treated region. Hence, we have compared two different laser applicators: a bare tip fiber (emitting light from the tip and forward) and a diffuser tip fiber (emitting light at 360° circumferentially from the side of the fiber). The experiments have been carried out percutaneously in a preclinical scenario (anesthetized pigs), under computed tomography (CT) guidance. The thermal effects of the two applicators have been assessed in terms of real-time temperature distribution, by means of an array of 40 fiber Bragg grating (FBG) sensors, and in terms of cavitation and ablation volumes, measured through CT post-temperature due to breathing motion has been analyzed and filtered out. Results show that the maximum temperature reached 50.5 °C for the bare tip fiber experiment (measured at 6.24 mm distance from the applicator) and 60.9 °C for the diffuser tip fiber experiment (measured at 5.23 mm distance from the applicator). The diffuser tip fiber allowed to achieve a more symmetrical heat distribution than the bare tip fiber, and without cavitation volume.Clinical Relevance-This work shows the analysis of the thermal effects of different laser fiber tips to improve laser ablation treatment. The results obtained in the preclinical scenario well represent the expected clinical outcome in the treatment of hepatic tumors. Moreover, these findings can be applied to other fields in which laser ablation is the optimal therapeutic choice, such as neurosurgery.