Pain after tonsillectomy remains the main issue of postoperative morbidity and the search for an effective post-tonsillectomy analgesic is of increasing relevance. The aim of this study was to evaluate the effectiveness of topical sucralfate during an early post-tonsillectomy period. Fifty patients of both genders from 6 to 58 years submitted to tonsillectomy or adenotonsillectomy were randomly included into either a sucralfate treatment group (N = 25) or into a control group (N = 25). Patients of the sucralfate group received topical sucralfate four times a day for 7 days. No topical treatment was applied to patients of the control group. A systemic analgesic was standardized. Post-tonsillectomy symptoms, including throat pain, odynophagia and otalgia, were evaluated during the period of seven postoperative days. Secondary outcomes were analgesic use, well being in general, return to regular daily activities, secondary hemorrhage and side effects of sucralfate. This study revealed that during the period of the second to seventh postoperative days average throat pain scores of the sucralfate using patients were significantly lower than those of the control group patients (p < 0.05); the same could be applied to odynophagia scores during the period of all seven postoperative days (p < 0.01) and otalgia scores from the 4th postoperative day (p < 0.05). The sucralfate group patients also had a significantly smaller need for analgesics, better scores of well being in general and early return to regular daily activities with no side effects of the treatment. Topical sucralfate could be recommended for the everyday clinical practice as a safe, adjuvant medicine of treatment during the period of the first post-tonsillectomy week.