Dissolution-reformation cycle of the passive oxide layer on the nickel-titanium (NiTi) orthodontic archwires was investigated, which has recently been recognized as one of the key parameters dictating the biocompatibility of archwires. Specifically, commercially available NiTi orthodontic archwires were immersed in artificial saliva solutions of different pH values (2.3, 3.3, and 4.3) for four different immersion periods: 1, 7, 14, and 30 days. Characterization of the virgin and tested samples revealed that the titanium oxide layer on the NiTi archwire surfaces exhibit a dissolution-reformation cycle within the first 14 days of the immersion period: the largest amount of Ni ion release occurred within the first week of immersion, while it significantly decreased during the reformation period from day 7 to day 14. Furthermore, the oxide layer reformation was catalyzed on the grooves within the peaks and valleys due to relatively larger surface energy of these regions, which eventually decreased the surface roughness significantly within the reformation period. Overall, the current results clearly demonstrate that the analyses of dissolution-reformation cycle of the oxide layer in orthodontic archwires, surface roughness, and ion release behavior constitute utmost importance in order to ensure both the highest degree of biocompatibility and an efficient medical treatment.