Objective. This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemostatically treated with a saline-coupled bipolar tissue sealer (SCBS) compared with traditional electrosurgical (ES) coagulation. Materials and Methods. Six cutaneous incisions were created on the dorsum of 28 adult male Yorkshire swine. The underlying muscle tissue was incised with a cold scalpel then treated with either SCBS (at 170 W) or traditional ES (at Coag 45 W). Time to hemostasis was recorded. Animals were humanely euthanized at day 2 and weeks 2, 3, or 8; treated tissue was harvested for histopathological evaluation. Results. After 8 weeks, the extent of wound healing was similar between SCBS and ES. Both devices controlled bleeding effectively; however, SCBS-treated wounds exhibited a greater depth of thermal effect over the first 3 weeks despite a shorter treatment time. Wounds treated with SCBS demonstrated fewer inflammatory markers at early time points but healed more slowly, with scores that lagged behind ES for collagen deposition, fibrous tissue maturity, extracellular matrix, and stage of healing. Myofiber regeneration notably increased in SCBS-treated wounds at weeks 2, 3, and 8. By the end of the 8-week recovery period, there were no significant differences in healing parameters between the 2 groups. Conclusions. Overall, both devices elicited similar progression of healing by 8 weeks. The SCBS produced a deeper thermal effect in a shorter treatment time and improved myofiber regeneration compared with ES and had an equivalent overall course of healing.