Rationale: Upper airway muscles function plays a major role in maintenance of the upper airway patency and contribute to the genesis of obstructive sleep apnea syndrome (OSAS). Preliminary results suggested that oropharyngeal exercises derived from speech therapy may be an effective treatment option for patients with moderate OSAS. Objective: To determine the impact of oropharyngeal exercises in patients with moderate OSAS. Measurements and main results: Thirty one moderate OSAS patients were randomized to 3 months of daily (~ 30 min) of sham therapy (n=15, control) or a set of oropharyngeal exercises (n=16), consisting of exercises involving the tongue, soft palate, and lateral pharyngeal wall. Anthropometric measurements, snoring frequency (range 0-4), intensity (1-3), Epworth daytime sleepiness (0-24), Pittsburgh sleep quality (0-21) questionnaires and full polysomnography were performed at baseline and at study conclusion. Body mass index and abdominal circumference of the entire group was 30.3±3.4 kg/m2 and 101.4±9.0 cm, respectively, and did not change significantly over the study period. No significant change occurred in the control group in all variables. In contrast, patients randomized to oropharyngeal exercises had a significant decrease (P<0.05) in neck circumference (39.6±3.6 vs. 38.5±4.0 cm), snoring frequency (4[4-4] vs. 3[1.5-3.5]), snoring intensity (3[3-4] vs. 1[1-2]), daytime sleepiness (14±5 vs. 8±6), sleep quality (10.2±3.7 vs. 6.9±2.5), and OSAS severity (apnea-hypopnea index - AHI, 22.4±4.8 vs. 13.7±8.5 events/hour). Changes in neck circumference correlated inversely with changes in AHI (r=0.59;P<0.001). Conclusions: Oropharyngeal exercises reduce significantly OSAS severity and symptoms and represent a promising treatment for moderate OSAS. Clinical Trial Registry: www.clinicaltrials.gov, i.d. = NCT 00660777