Purpose: Little is known about gender differences in the treatment of pain after motor vehicle collisions (MVCs) in an emergency department (ED). We aimed to describe gender differences in pain experiences and treatment, specifically the use of opioids and benzodiazepines after ED discharge, for MVC-related pain. Methods: This was a secondary analysis of previously collected data from the CRASH Injury studies. We included patients who were seen and discharged from an ED after an MVC and who were enrolled in 1 of 2 multicenter longitudinal prospective cohort studies (1 black/non-Hispanic and 1 white/non-Hispanic). First, we compared the experience of pain as defined by self-reported moderate-to-severe axial pain, widespread pain, number of somatic symptoms, pain catastrophizing, and peritraumatic distress between women and men using bivariate analyses. We then determined whether there were gender differences in the receipt of prescription medications for post-MVC pain symptoms (opioids and benzodiazepines) using multivariate logistic regression adjusting for demographic characteristics, pain, and collision characteristics. Findings: In total, 1878 patients were included: 61.4% were women. More women reported severe symptoms on the pain catastrophizing scale (36.8% vs 31.0%; P = 0.032) and peritraumatic distress following the MVC (59.7% vs 42.5%; P < 0.001), and women reported more somatic symptoms than men (median, 3.9; interquartile range, 3.7-4.0 vs median, 3.3; interquartile range, 3.1-3.5; P < 0.001). Unadjusted, similar proportions of women and men were given opioids (29.2% vs 29.7%; P = 0.84). After adjusting for covariates, women and men remained equally likely to receive a prescription for opioids (relative risk = 0.83; 95% confidence interval, 0.58–1.19). Women were less likely than men to receive a benzodiazepine at discharge from an ED (relative risk = 0.53; 95% confidence interval, 0.32–0.88). Implications: In a large, multicenter study of ED patients treated for MVC, there were gender differences in the acute psychological response to MVC with women reporting more psychological and somatic symptoms. Women and men were equally likely to receive opioid prescriptions at discharge. Future research should investigate potential gender-specific interventions to reduce both posttraumatic distress and the risk of developing negative long-term outcomes like chronic pain.