The goal of this study was to determine whether the acute analgesic effects of alcohol intake are moderated by acute alcohol tolerance, characterized by differing subjective and neurobehavioral effects of a given blood alcohol concentration (BAC) depending on whether BAC is rising or falling. Twenty-nine healthy drinkers (20 women) completed two laboratory sessions in which they consumed a study beverage: active alcohol (target BAC= .08 g/dl) and placebo. Acute alcohol tolerance was assessed by examining the main and interactive effects of beverage condition and assessment limb (ascending vs. descending) on quantitative sensory testing measures collected using slowly ramping heat stimuli and perceived relief ratings at comparable breath alcohol concentrations on the ascending and descending limbs. BAC limb moderated the effect of condition on pain threshold, such that the threshold was significantly elevated in the alcohol condition on the ascending limb. The alcohol condition produced greater ratings of perceived pain relief than the placebo condition, and pain relief ratings were greater on the ascending versus descending limb of the BAC curve. Alcohol intake did not significantly affect pain tolerance or aftersensation ratings on either BAC limb. This study provides initial experimental evidence that alcohol's analgesic and pain-relieving effects are subject to acute tolerance following acute alcohol intake. These findings suggest that self-medicating pain via alcohol intake may be associated with high-risk drinking topography, increasing the risk for alcohol-related consequences. Further research is needed to determine if these effects extend to the context of clinical and chronic pain.