<p>Headaches are among the most common neurological disorders, often leading to significant disability and reduced quality of life^1,2. However, much remains unknown about the triggers that precipitate headaches³. Coffee is one of the most widely consumed beverages worldwide, and coffee withdrawal is thought to be associated with headache^4,5. However, research linking caffeine withdrawal to headache in healthy adult populations is largely limited to observational studies prone to confounding or single snapshot assessments prone to recall bias^6–8. While small, near-term randomized trials have been conducted, these generally are done in artificial study-based settings (rather than among ambulatory individuals) and fail to capture repeated events that best represent real-life circumstances^9,10. We sought to leverage a prospective, randomized, case-crossover trial to assess acute relationships between caffeine withdrawal and headaches among healthy individuals¹¹. Here, we show that among regular caffeinated coffee consumers, caffeine avoidance likely contributes to headaches. When headaches are present, caffeine avoidance was also associated with increased headache severity. These results suggest that headache, commonly experienced by a substantial proportion of the population, may often occur as a consequence of caffeinated coffee withdrawal. Together, these findings may inform behaviors and recommendations regarding coffee consumption and minimizing headache burden on a day-to-day basis.</p>