Objective: In Phase I, we demonstrated the safety and efficacy of the pulsed 2.94 micron Er:YAG laser for caries removal, cavity preparation and laser etching utilizing in vivo teeth scheduled for removal to quantitatively verify the safety of the product for up to one year following treatment. Phase II was a continuation of this study evaluating in vivo teeth to verify the safety and efficacy of the Er:YAG in a long-term follow-up study. Methods: We randomly divided the patients into two groups: a laser group and a control group, which employed the high speed drill. The investigators rated clinical efficacy by several criteria, evaluated pain and measured pulpal vitality up to two years following treatment. This phase consisted of 512 procedures that made up the laser group and 357 procedures that made up the control group. Conclusions: The results from this phase showed that the Er:YAG laser was able to perform as well as, if not better than, the drill in caries removal, cavity preparation, and acid etching alone. Use of the laser virtually eliminated the need for anesthesia. The Er:YAG laser is safe and efficacious for removal of caries, cavity preparation and etching prior to acid etching.