The aim of this study was to assess the impact of orthodontic treatment with orthodontic aligners (OAs) and fixed appliances (FAs) on oral health-related quality of life (OHRQoL). This parallel randomized clinical trial included 40 male and female patients aged 13 to 35 years diagnosed with Angle's Class I malocclusion. Participants were assigned to two groups: OA (n = 20) and FA (n = 20). OHRQoL was assessed using the Brazilian OHIP-14, which was administered before treatment (T0), at 1 month (T1), 6 months (T2), and 12 months (T3) after treatment initiation. Data were analyzed using the independent t test, the chi-square test, the Mann-Whitney test, and Friedman test (p < 0.05). FAs had a significantly (p < 0.05) higher impact on OHRQoL at T1 in terms of functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, and overall score. Within-group comparison showed higher scores for the FA group in comparison to the OA group. Functional limitation scores were higher at T1 than at T0 (p = 0.034), while physical pain scores were higher at T1 compared to T0 (p = 0.034) and T2 (p = 0.010). Psychological discomfort scores were higher at T1 than at T2 (p = 0.015). Physical disability scores were higher at T1 compared to T0 (p = 0.008). Overall scores were higher at T1 than at T2 (p = 0.003). No significant changes were observed in the OA within-group comparison. Patients treated with OAs had less impact on OHRQoL compared to those treated with FAs in the first month. There was no difference between the groups at the 6-month follow-up.