Gastroeophageal reflux is a condition in which the acidified liquid content of the stomach backs up into the esophagus. The antiacid magaldrate and prokinetic domperidone are two drugs clinically used for the treatment of gastroesophageal reflux symptoms. However, the evidence of a superior effectiveness of this combination in comparison with individual drugs is lacking. A double-blind, randomized and comparative clinical trial study was designed to characterize the efficacy and safety of a fixed dose combination of magaldrate (800 mg)/domperidone (10 mg) against domperidone alone (10 mg), in patients with gastroesophageal reflux symptoms. One hundred patients with gastroesophageal reflux diagnosed by Carlsson scale were randomized to receive a chewable tablet of a fixed dose of magaldrate/domperidone combination or domperidone alone four times each day during a month. Magaldrate/domperidone combination showed a superior efficacy to decrease global esophageal (pyrosis, regurgitation, dysphagia, hiccup, gastroparesis, sialorrhea, globus pharyngeus and nausea) and extraesophageal (chronic cough, hoarseness, asthmatiform syndrome, laryngitis, pharyngitis, halitosis and chest pain) reflux symptoms than domperidone alone. In addition, magaldrate/domperidone combination improved in a statistically manner the quality of life of patients with gastroesophageal reflux respect to monotherapy, and more patients perceived the combination as a better treatment. Both treatments were well tolerated. Data suggest that oral magaldrate/domperidone mixture could be a better option in the treatment of gastroesophageal reflux symptoms than only domperidone.