Objective: A saliva substitute based on polyglycerylmethacrylate, lactoperoxidase, and glucose oxidase (Oral Balance) has been developed. The aim of this study was to evaluate the effect of Oral Balance on the dryness-related oral complaints in patients suffering from irradiation-induced xerostomia. Method and materials: The efficacy of Oral Balance on the dryness-related complaints of 28 patients was assessed by means of self-administered questionnaires. Each patient completed an initial questionnaire about dryness-related symptoms and then was given the moistening gel. The patients were instructed to apply the gel as often as desired. After 2 weeks and 3 months, the patients were asked to complete a progress questionnaire. The severity of xerostomia was measured with a saliva absorption method. Results: All patients suffered from moderate-to-severe xerostomia, the severity of which did not change during the experimental period. Three patients did not complete the study. In the other 25 patients, the application of Oral Balance tended to diminish the sensation of oral dryness and improve oral functioning. Statistically significant reduction of the dryness-related complaints was observed only in the patients suffering from severe xerostomia. Conclusion: Use of Oral Balance is of potential benefit in patients suffering from severe xerostomia.