Objective The study was performed to assess the risk of at-home and in-office bleaching procedures, and to recognise potential predictors for side effects. Design Multi-centre, questionnaire-based prospective study with follow-ups at around 14 days and around one year post-treatment. Setting General practices and university clinics during the years 2007‑2009 in Scandinavia. Subjects Patients with tooth bleaching as part of the treatment plan. Results The prevalence of experienced tooth sensitivity at first follow-up was independent of bleaching procedure (at-home = 50.3% [n = 143]; in-office = 39.3% [n = 28]; p >0.05; 95% CI [OR]: 0.198‑1.102) whereas prevalence of gingival irritation was higher after in-office treatment (at-home = 14.0%; in-office = 35.7%; p <0.05) (mean age: 37.3 years; 73.7% women; n = 171). At the second follow-up, two and three patients reported side effects attributed to the bleaching treatment in the at-home and in-office groups, respectively. Predictors for side effects were tooth sensitivity, surface loss and gingivitis when observed at inclusion. Treatment-related predictors were bleaching concentration and contact between tray and gingiva. Conclusions Bleaching treatment, irrespective of method, caused a high prevalence of side effects. Patients associated with the predictors at inclusion mentioned above should be notified of the risk for side effects and treated only if bleaching is indicated based on a proper diagnosis.