Background and objectives The prevalence of pain syndromes that affect the territories innervated by the trigeminal nerve, such as headaches, is one of the highest and ranks second only to low back pain. A potential mechanism underlying this high prevalence may be a relatively weak endogenous pain modulation of trigeminal pain. Here, we sought to systematically compare endogenous pain modulation capabilities in the trigeminal region to those of extra-trigeminal regions in healthy subjects. Methods Healthy, pain free subjects (n = 17) underwent a battery of quantitative sensory testing to assess endogenous pain inhibition and pain enhancement efficiencies within and outside the trigeminal innervated region. Measurements included conditioned pain modulation (CPM), temporal summation of pain (TSP) and spatial summation of pain (SSP). Results Testing configurations that included trigeminal-innervated body regions displayed significantly weaker CPM when compared to extra-trigeminal innervated areas. SSP magnitude was smaller in the ophthalmic trigeminal innervation when compared to other body regions. TSP magnitude was not different between the different body regions tested. Conclusions Our findings point to regional differences in endogenous pain inhibition and suggest that in otherwise healthy individuals, the trigeminal innervation is subjected to a weaker inhibitory pain control than other body regions. Such weaker endogenous pain control could play, at least in part, a role in mediating the high prevalence of trigeminal-related pain syndromes, including primary headaches and TMD pain.