Introduction There is an increasing research interest in quality of life issues in orthodontics. In this study, we aimed to investigate changes in oral health related quality of life (OHRQoL) among adults during fixed orthodontic appliance therapy (FOAT). Methods Two hundred thirty-two adult patients were enrolled from a consecutive sample at a university dental hospital. OHRQoL was assessed by 2 standardized instruments (OHIP-14 and OHQoL-UK) at 4 times: before treatment (T0), 6 months after bonding and banding (T1), 12 months after bonding and banding (T2), and 18 months after bonding and banding (T3). Friedman 2-way analysis of variance (ANOVA) and Wilcoxon signed rank tests were used to compare the relative changes of OHRQoL among the different time points. Results Significant changes in the summary scores of both the OHIP-14 and OHQoL-UK were observed during fixed orthodontic treatment ( P <0.001). There were significant OHRQoL deteriorations at T1 and T2 compared with T0; these were reflected by summary scores of both the OHIP-14 and OHQoL-UK as well as some of their domain scores ( P <0.05). However, at T3, the OHIP-14 suggested deterioration in OHRQoL, but the OHQoL-UK suggested improvement in OHRQoL. Conclusions Changes in OHRQoL occur during fixed orthodontic appliance therapy. In the early phase of treatment, the greatest deterioration in OHRQoL occurs. With ongoing treatment, the detrimental effects to OHRQoL are reduced.