Introduction: Tongue thrust is a frequent clinical condition characterized by abnormal patterns of movements and altered tongue posture on the mouth floor. It might contribute to determining alterations in the maxillofacial morphology and in the development of malocclusion. Several therapeutic options are available for treatment. In particular, the orofacial myofunctional therapy (OMT) is frequently adopted even if only few studies have analyzed its efficacy using validated instruments and no information is available regarding the effect of dentition on the results obtained with OMT. Objective: To evaluate the effect of OMT through a validated instrument and explore the role of dentition on its efficacy. Methods: A total of 22 consecutive patients with tongue thrust were enrolled. According to the presence of mixed or complete dentition, the cohort of patients was divided into 2 groups. Each patient underwent OMT according to the Garliner method (10 weekly sessions of 45 min each in hospital and daily exercises at home). The efficacy of OMT was evaluated using the Orofacial Myofunctional Evaluation with Scores (OMES), a validated protocol developed for the assessment of orofacial myofunctional disorders, and the Iowa Oral Performance Instrument (IOPI) to measure the peak isometric pressure exerted by the anterior and posterior part of the tongue. Both OMES and IOPI were administered before and at the end of the treatment. Results: A significant improvement in the OMES scores was demonstrated after OMT. No significant differences between the patients with intermediate and mixed dentition obtained in both the pre- and post-treatment conditions were demonstrated in the OMES scores. Similarly, a significant increase in the peak isometric tongue pressure in both the anterior and posterior parts of the tongue was demonstrated after OMT in the groups. No differences between the two groups in both the pre- and post-treatment conditions were demonstrated in the IOPI scores. Conclusions: OMT improves orofacial motricity and tongue strength in patients with tongue thrust regardless of the type of dentition.