Human studies have reported sex differences in analgesia and side effects with exogenous μ and κ opioids; however, data are mixed regarding the direction and magnitude of effects. The variable pattern of sex differences in opioid analgesia can be attributed to a variety of methodological factors, including the specific opioid agent(s) studied, the pain assay used, and characteristics of the study sample. In order to address these issues, the present study used a randomized, double blind, mixed design to investigate sex differences in morphine and butorphanol analgesia using multiple pain assays. Twenty-eight healthy young males (n=13) and females (n=15) underwent thermal, pressure, and ischemic pain testing before and after receiving an IV bolus of morphine (0.08 mg/kg), butorphanol (0.016 mg/kg) and saline placebo. All participants received each drug condition on separate occasions in random counterbalanced order. Consistent with previous studies, preliminary analyses revealed significant analgesic effects of both medications across all pain stimuli. In addition, some sex-by-drug interactions emerged. For example, males derived better analgesia with butorphanol than morphine in measures of heat pain tolerance. For thermal temporal summation, when sex differences emerged, it was often in the direction of females deriving more analgesia from morphine, and males exhibiting better analgesia with butorphanol. However, the pattern of effects varied according to stimulus temperature (i.e., 46°C, 48°C, 50°C). Both sexes derived more analgesia from butorphanol on all pressure pain assays (i.e., trapezius, masseter and ulna). Ischemic pain tolerance revealed a significant (p<0.05) sex-by-drug interaction, with females responding more favorably to morphine and males to butorphanol. On balance, these preliminary results demonstrate sex differences in opioid analgesia that vary according to assay and medication type. The results have implications for considering sex and pain characteristics when determining equianalgesic doses, especially when switching between opioids with different receptor subtype targets.