Background: Recently it has been described that 5-phosphodiesterase (5-PDE) inhibitors produce esophageal smooth muscle relaxation through the increase and extension of the inhibitory activity of cGMP. Some studies have shown that sildenafil alters LES function, amplitude and velocity of esophageal peristaltic contractions but not induce gastro-oesophageal reflux. Tadalafil is a 5-PDE inhibitor that has a half-life of 18 hours and its plasma clearance can take up to 72 hours. Thus, in this study we hypothesize that tadalafil induce a sustained and prolonged effect in esophageal motor function. Objective: To evaluate the effect of a single dose of 20 mgs of tadalafil on esophageal motility and the lower esophageal sphincter in healthy volunteers and patients with spastic disorders of the esophagus. Materials and Methods: In this study, we included 10 healthy volunteers (6 men, mean age 27.5 years) and 10 patients (6 with type II achalasia, 2 with type III achalasia and 2 with hypertensive peristalsis [5 men, mean age 45 years]). At baseline, in all subjects a highresolution manometry (Given, Yoqneam, Israel) was performed. Baseline HRM included 10 swallows of 5ml of NaCl; then all subjects received 20 mgs of tadalafil (Cialis, LillyICOS, Washington, U.S.) and the catheter was left in place 2 hours. At 15, 30, 45, 60 and 120 minutes after the tadalafil dose, 5 swallows of 5 ml were performed. Blood pressure and heart rate was recorded continuously. 24 hours and 48 hours after de tadalafil dose, all subjects return to the lab to repeat HRM. We measure LES and esophageal motility function according to the Chicago II classification parameters. Results: In controls, 60 minutes after tadalafil administration a decrease in basal resting pressure of the LES was recorded (18.8 ± 4 mmHg ,p = 0.019) and this decrease was progressive at, 2 hours, 24 and 48 hours (Figure 1). The lowest point of pressure was reached after 48 hours. The pressure reduction was observed in all but one subject. The average amplitude of esophageal contraction significantly decreased in all 3 segments after 45 minutes of the administration of tadalafil, and its recovery began at 48 hours (Figure 2 p ,0.05). Similar findings were recorded in 8 of the 10 patients. In addition, 6 patients reported improvement of dysphagia at 24 and 48 hours, and in threes case this improvement lasted up to 72 hours. In all cases there were not cardiovascular effects with the administration of tadalafil. The most common side adverse effect reported was mild headache. Conclusions: Tadalafil is a 5-PDE that induce a prolonged and sustained effect on esophageal contractions, is well tolerated and it could be a promising drug in the management of esophageal motor disorders.