While previous research has indicated that the relative efficacy of attentional strategies on pain may be influenced by anxiety sensitivity (AS) and sex, no study appears to have examined this within the context of an emotion-focus versus distraction paradigm. The present study compared the effect of attentional emotion-focus and distraction instructions on pain response with noxious heat stimulation in 114 healthy adults (62 women and 52 men) varying in levels of AS. Results indicated that men reported a significantly higher mean tolerance time than women. Moderated regression analysis also revealed a significant strategy × anxiety sensitivity × sex interaction on pain tolerance. For those low in AS, relative efficacy was dependent upon sex, with distraction superior to emotion-focusing in women, but with strategies equivalent in men. For those high in AS, however, distraction resulted in uniformly greater pain tolerance than attentional emotion-focusing. These results indicate that AS and sex may be influential in determining the relative effectiveness of distraction and emotion-based attentional strategies for pain management.