Radiotherapy (RT) plays a key role in the management of head and neck cancer (HNC), especially in locally advanced disease. Patients undergoing head and neck RT, especially elderly ones, are suffering from low and labile blood pressure (BP) during the treatment. They complain of weakness and fatigue and are prone to recurrent falls. The aim of this study was to characterize BP changes during RT period. Patients with HNC, receiving radiation to the neck, were recruited from Sheba medical center RT unit. Office BP, orthostatic measurements, 24-hour ambulatory BP monitoring, body weight, and metabolic parameters were measured at baseline after 30 days and after 90 days from beginning of therapy. Nineteen patients (17 males), 64 ± 12 years old were recruited. Nine hypertensive patients continued their antihypertensive treatment during the study. Office systolic BP and diastolic BP decreased significantly after 30 days (128 ± 4/80 ± 3 to 122 ± 3/74 ± 3 mm Hg; P < 0.05). Average 24-hour BP values after 30 days of RT decreased from 130 ± 3/76 ± 2 to 123 ± 3/71 ± 2 mm Hg; P < 0.05. A similar trend was observed for day and night BP levels. Decrease in office and ambulatory BP was sustained for several months after RT completion. No orthostasis was observed during the study period. Patient lost weight significantly during the study period. However, BP changes were independent of weight loss. There is a significant and sustained BP reduction after head and neck RT, without orthostatic changes. Clinicians should be aware of this phenomenon and consider treatment adaption accordingly.