Statement of Purpose: Sutures, staple, and conventional glues are commonly used to approximate tissue edges in surgery and wound healing. However, poor strength, infection, dehiscence, leakage, and / or acute inflammation are common complications associated with these methods. Laser-activated tissue sealing, in which, laser light energy is used to facilitate biomaterial incorporation with the tissue, provides an alternative approach for wound closure. Traditionally, light-absorbing chromophores and nanoparticles have been employed for converting near infrared (NIR) laser light to heat, resulting in the photothermal fusion of the sealant biomaterial with soft tissues. We now demonstrate a novel approach for sealing tissues without the need for chromophores using mid infrared (midIR) laser light. We characterized the absorption of midIR light by several different biomaterials and investigated the rise in local temperature at different laser powers. Optimal operating conditions were employed for midIR based photothermal sealing of incised / ruptured tissue ex vivo and using different skin surgical models in live mice. Recovery of mechanical properties including tensile strength and burst and leak pressures, in concert with histopathology analyses, were employed to determine the efficacy of the seal. The effect of midIR light on cell and tissue viability was also determined. Our results demonstrate that midIR lasers can be used for rapid sealing of soft tissues using conventional biomaterials without the need for chromophores or nanoparticles, which is a significant advantage for rapidly translating this technology in the clinic.