Purpose: To characterize temperature fields and tissue damage profiles of large-volume hyperthermia (HT) induced by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) in deep and superficial targets in vivo in a porcine model. Methods: Nineteen HT sessions were performed in vivo with a commercial MRgHIFU system (Sonalleve V R V2, Profound Medical Inc., Mississauga, ON, Canada) in hind leg muscles of eight pigs with temperature fields of cross-sectional diameter of 58-mm. Temperature statistics evaluated in the target region-of-interest (tROI) included accuracy, temporal variation, and uniformity. The impact of the number and location of imaging planes for feedback-based temperature control were investigated. Temperature fields were characterized by time-in-range (TIR, the duration each voxel stays within 40-45 C) maps. Tissue damage was characterized by contrast-enhanced MRI, and macroscopic and histopathological analysis. The performance of the Sonalleve V R system was benchmarked against a commercial phantom. Results: Across all HT sessions, the mean difference between the average temperature (T avg) and the desired temperature was À0.4 ± 0.5 C; the standard deviation of temperature 1.2 ± 0.2 C; the temporal variation of T avg for 30-min HT was 0.6 ± 0.2 C, and the temperature uniformity was 1.5 ± 0.2 C. A difference of 2.2-cm (in pig) and 1.5-cm (in phantom) in TIR dimensions was observed when applying feedback-based plane(s) at different locations. Histopathology showed 62.5% of examined HT sessions presenting myofiber degeneration/necrosis within the target volume. Conclusion: Large-volume MRgHIFU-mediated HT was successfully implemented and characterized in a porcine model in deep and superficial targets in vivo with heating distributions modifiable by userdefinable parameters.