OBJECTIVE Orthodontic appliances are considered to be highly biocompatible although adverse effects attributed to the release of nickel ions (Ni(2+)) have been documented. Self-ligating brackets have grown in popularity for economic reasons and supposed friction reduction. The aim of the present prospective cohort study was therefore to determine salivary Ni(2+) concentrations in patients undergoing orthodontic treatment with self-ligating fixed appliances. MATERIALS AND METHODS A group of 30 patients between 10 and 13 years of age were treated with self-ligating brackets (SmartClip™), molar bands, and nickel-titanium (NiTi) archwires. Unstimulated saliva samples were collected after different time points (before treatment, after self-ligating bracket and band placement, before archwire insertion, after archwire insertion, and finally 4 and 8 weeks afterwards) and analyzed with an ICP mass spectrometer followed by generalized estimating equation modelling with α = 5 %. RESULTS The baseline median salivary Ni(2+) concentration was 21.85 µg/l, while the Ni(2+) concentrations at the following visits ranged between 13.73 and 85.34 µg/l. Significant increases in Ni(2+) levels compared to the baseline levels were detected after band/bracket placement [+59.76 µg/l; 95 % confidence interval (CI) 44.88-74.64 µg/l; P < 0.001] and after archwire insertion (+53.55 µg/l; 95 % CI 25.57-81.52 µg/l; P < 0.001). After 4 weeks, Ni(2+) concentrations returned to initial control levels or were lower. CONCLUSION Self-ligating orthodontic appliances may affect salivary Ni(2+) concentrations in vivo over the short term. However, levels resembled those documented in conjunction with conventional bracket use and remained below the daily dietary Ni intake.