The purpose of this study was to investigate the impact of botulinum toxin (BoNT) treatment on the quality of life (QoL) for patients with prominent lingual dystonia (LD) using a disease-specific questionnaire, the oromandibular dystonia questionnaire-25 (OMDQ-25). This is a prospective, observational study of a cohort of 30 patients treated with BoNT injections for LD, with or without concurrent jaw dystonia. Primary efficacy outcome was the absolute difference between total OMDQ-25 baseline score and total OMDQ-25 scores 4 and 8 weeks after the treatment. Safety outcome was the occurrence of adverse effects. The mean total OMDQ-25 baseline score was 46.8 ± 17.8. After BoNT treatment, there was a significant reduction in the mean total OMDQ-25 score at 4 weeks (38.2 ± 17.6; p = 0.004), as well as at 8 weeks (39.6 ± 18.1; p = 0.008). At the multiple regression analysis, a jaw deviation pattern (JDD) and high questionnaire baseline total score were detected as predictors of a better outcome, whilst associated jaw tremor was a predictor of poor outcome. In patients with JDD, jaw-opening muscles were more frequently injected and genioglossus less frequently than in patients without JDD. No major adverse events were detected. A consistent and measurable improvement in QoL, with good safety and tolerability, can be achieved in patients with prominent LD by injecting BoNT into genioglossus and/or other muscles of the oromandibular region.