Development of a noninvasive vasectomy technique may eliminate male fear of complications (incision, bleeding, infection, and scrotal pain) and result in a more popular procedure. These studies build off previous studies that report the ability to thermally target tissue substructures with near infrared laser radiation while maintaining a healthy superficial layer of tissue through active surface cooling. Initial studies showed the ability to increase the working depth compared to that of common dermatological procedures and the translation into an ex vivo canine model targeting the vas deferens in a noninvasive laser vasectomy. Laser and cooling parameter optimization was required to determine the best possible wavelength for a safe transition to an in vivo canine model. Optical clearing agents were investigated as a mechanism to decrease tissue scattering during in vivo procedures to increase optical penetration depth and reduce the overall power required. Optical and thermal computer models were developed to determine the efficacy for a successful transition into a human model. Common clinical imaging modalities (ultrasound, high frequency ultrasound, and optical coherence tomography) were tested as possible candidates for real-time imaging feedback to determine surgical success. Finally, a noninvasive laser vasectomy prototype clamp incorporating laser, cooling, and control in a single package was designed and tested in vivo. Occlusion of the canine vas deferens able to withstand physiological burst pressures measured post-operative was shown during acute and chronic studies. This procedure is ready for azoospermia and recanalization studies in a clinical setting.