Neuromodulation of afferent cranial nerve activity is useful for alleviating migraine and trigeminal pain, which is often poorly managed by pharmacologic interventions. Synchronous stimulation of trigeminal, vagal, glossopharyngeal and cervical nerve afferents shows promise for such intervention, but potential effects on the cardiovascular system must be considered, since several of the cranial nerves exert significant effects on heart rate and blood pressure. The objective was to determine changes in heart rate (HR), HR variability, and blood pressure at two stimulation amplitude levels to cranial nerves. Fourteen subjects with confirmed migraine or trigeminal neuropathy pain were fitted with vibrating devices placed in the ear canals bilaterally. Heart rate (beats/min), inter‐beat intervals (RR, msec), beat‐by‐beat systolic and diastolic blood pressures (mm Hg) were measured continuously during baseline, and during low and high amplitude, and post stimulation periods. Mean HR declined during low and high stimulation; baseline, low, high, and post‐session were 76, 73, 72, 74 bpm respectively, p < .001 (Single‐Factor Repeated Measures ANOVA), with lengthening of mean RR intervals (802, 829, 839, 821 msec, respectively). HR and RR intervals recovered during the post stimulation period to pre‐session values. Mean systolic and diastolic blood pressure declined with stimulation (mean systolic: 130, 124, 125, and 130 mm Hg, respectively; mean diastolic: 79, 77, 77, and 79 mm Hg, respectively), and recovered post‐stimulation. HR variability patterns changed from pronounced baseline variation from respiratory and slower variation influences to reduced slower, but increased respiratory‐related variation, representing a shift to parasympathetic influences during stimulation; these values recovered post‐stimulation. No instances of potentially dangerous bradycardia or tachycardia, or extreme changes in blood pressure appeared. We conclude that HR, HR variability, and blood pressure change during stimulation, and move toward values considered “protective.”