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1. Although the analgesic effect of opioids on experimental cold pressor (CP) pain has been well demonstrated, the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs) on experimental CP pain has been less reliable, a finding complicated by inconsistencies in how CP analgesic effect is measured. 2. In the present study, a clinically relevant CP response of pain tolerance was used to assess the previously undescribed analgesic efficacy of the potent NSAID ketorolac (10 mg, p.o.), on CP pain across gender in a sample of normal subjects (n = 50). 3. Using a placebo-controlled crossover design, neither a main nor interaction effect for ketorolac on CP pain tolerance was detected. When examined by gender, male subjects exhibited a large placebo response to CP pain under study conditions, whereas women (albeit less pain tolerant at baseline) evidenced no placebo effect but a modest-to-good NSAID analgesic response. 4. Findings on the gender-specific placebo and analgesic NSAID response, integrated with the current literature, indicate that the lack of NSAID analgesic efficacy in the CP pain model may be related to unexamined and differential effects of how gender affects NSAID analgesic effect.