The aim was to assess the composition of released metal ions from fixed orthodontic appliances both in an in vitro and in vivo setting and to compare their quantities to evaluate any possible health risks associated with them. For the in vitro setting, a set of 24 as-received sterile SS brackets, 2 SS sterile archwires, and 2 NiTi sterile archwires were aged for 90 days in artificial saliva, and released metal ion concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS), using matrix-matched standards for calibration. For the in vivo setting, 15 brackets, 15 SS, and 15 NiTi archwires were retrieved after 90 days of intraoral exposure in 15 subjects. Debris composition on each part of the orthodontic appliance was assessed using scanning electron microscopy with energy dispersive spectroscopy (SEM/EDS). The present study evidenced a difference in the composition of released metal ions from fixed orthodontic appliances detected in an in vitro and in vivo setting. Generally, the relative content of metal ions was higher in the retrieved debris than that released in artificial saliva. The concentration of released metal ions from all tested alloys was below the upper recommended limit of daily intake; however, possible local effects in terms of hypersensitivity due to their accumulation in the debris cannot be excluded even with such concentrations.