Acupuncture is an alternative treatment for wide spectrum chronic pain. However, its validity remains controversial due to the disputed efficacy assessed in various clinical studies. Moreover, variability amongst individuals complicates the predictability of outcome, which impedes the integration of acupuncture into mainstream pain management programs. In light of our previous finding that the analgesic effect of acupuncture is mediated by adenosine A1 receptor activation at the acupuncture point, we here report that in acute and chronic animal pain models, oral intake of caffeine, a potent adenosine receptor antagonist, interferes with acupuncture analgesia, even at a low dose. Local administration of caffeine at the acupuncture point was sufficient to eliminate the analgesic effect, dismissing the systemic action of caffeine. Such interference was reversible, as caffeine withdrawal fully restored the efficacy of acupuncture by the next day, and long-term exposure to caffeine did not alter A1 receptor expression at the acupuncture point. Combined, these data indicate that a trace amount of caffeine can reversibly block the analgesic effects of acupuncture, and controlling caffeine consumption during acupuncture may improve pain management outcomes.