Nickel (Ni) is a potent sensitizer and may induce innate and adaptive immune responses. Ni is an important component of orthodontic appliances (8–50wt%). Due to chemical and mechanical factors in the oral environment, Ni is released from these appliances. Retention wires are in situ for a long period of time.To quantitatively evaluate the influence of mechanical loading and pH on the nickel release from orthodontic retention wires.Five different types of multi-stranded wires (Original Wildcat, Noninium, Lingual retainer, Dentaflex 3-s, Dentaflex 6-s), were submersed for 24h in either 10ml of distilled water or lactic acid, both submitted to cyclic loading in a 3-point bending test (0×, 1000×, 10,000×). The solutions were analyzed by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS), and the data was statistically analyzed (ANOVA, p<0.05).Mechanical loading has a strong effect on the Ni release from orthodontic retention wires, especially in distilled water. Acidity has more impact on Ni release when compared to mechanical loading. Manganese-steel “Ni-free” wires released quantifiable amounts of Ni due to trace elements of Ni within the wire.All investigated wires release considerable amounts of Ni to which exposure may have biological implications.