Trismus is a common symptom often related to the treatment for head and neck cancer and to temporomandibular disorders. The purpose of the present study was to measure the impact of trismus on health-related quality of life (HRQOL) and mental health in patients with head and neck cancer and temporomandibular disorder. We used the criteria for trismus of maximum interincisal opening (MIO) ≤35 mm and the study subjects responded to the following instruments: the Gothenburg Trismus Questionnaire (GTQ), the Short-Form 36 Health Survey (SF-36), and the Hospital Anxiety and Depression Scale (HADS). The study also comprised an age-matched and sex-matched control group without trismus. Patients with trismus reported significantly more dysfunction in all GTQ domains and more facial pain compared to the control group. The patients with head and neck cancer and trismus scored significantly lower on all SF-36 domains except general health compared to the control group, and the patients with temporomandibular disorder with trismus scored significantly lower in 3 of the 8 domains in SF-36. According to the HADS, a greater proportion of patients with head and neck cancer with trismus displayed more depression compared to the control group. The results showed that trismus is associated with a significant impact on HRQOL and that patients with trismus should be approached in a holistic way with respect for the underlying cause, treating not only the physical aspects of trismus but also addressing the patients' mental health.