RATIONALE: Pain and nicotine use are co-occurring conditions with a significant impact on health. Experimental evidence supports an acute analgesic effect of nicotine which may reinforce nicotine use among those with chronic pain. Evidence for nicotine analgesia have primarily been gathered in combustible cigarette users and have not been extended to electronic nicotine delivery systems (ENDS or vaping). Furthermore, the mechanisms of nicotine analgesia in humans are not well understood. OBJECTIVES: Assess the effect of acute vaped nicotine on subjective and behavioral indices of pain sensitivity using three tasks designed to probe distinct mechanisms of analgesia. METHODS: This study recruited ENDS users (N = 86) to undergo a paced vaping protocol followed by pain tasks in counterbalanced order. Across four sessions, participants vaped e-liquid containing nicotine or placebo, and flavor or no-flavor in a 2 × 2 within-subject design. Assessments included cold pressor, submaximal effort tourniquet to induce ischemic pain, and temporal summation of heat pain, an index of central sensitization. RESULTS: Compared to placebo, nicotine increased cold pressor pain tolerance (η CONCLUSIONS: Consistent with research from tobacco smoking, analgesia may be reinforcing and contribute to nicotine dependence among ENDS users. More research on sex differences is warranted.