Objectives <p>The aim of the study was to investigate the effect of preventive exercise therapy on radiation-induced trismus in head and neck cancer.</p> Materials and methods <p>Eighty-nine patients (<i>n</i> = 89) with newly diagnosed head and neck cancer were included and randomized to either the preventive exercise intervention group (<i>n</i> = 45) or the control group. (<i>n</i> = 44). The intervention group was instructed to perform jaw opening exercises once daily.</p> Results <p>No differences were found in mouth opening capacity between the intervention and the control groups in the first year after oncological treatment. At the 6-month follow-up, the prevalence of trismus was 7% and 19% in the intervention and the control groups, respectively, and at the 12-month follow-up, 7% and 3%, respectively; these differences were not statistically significant.</p> Conclusion <p>Preventive exercise was not effective in improving trismus and mouth opening-related outcomes in this randomized study. A surprisingly low prevalence of trismus was seen in both groups in the first year after radiotherapy.</p> Clinical relevance <p>There is reason to believe that newer radiotherapy regimens have reduced radiation trismus in HNC. Although prophylactic intervention does not appear to influence mouth opening capacity, it is important to carefully monitor mouth opening in patients undergoing radiotherapy for HNC. Early detection of a reduction in MIO can permit early initiation of exercise interventions for trismus.</p>