Chronic pain and PTSD are known to hold substantial comorbidity following traumatic injury. Although pharmacological agents have been examined in the treatment of pain and PTSD individually, little is known regarding the relationship of medication use with functioning in patients with comorbid conditions. This research examined the relationships of pain, PTSD, and medication use across physical and psychosocial functioning in patients with chronic pain following motor vehicle injury (N=234). Separate analyses were conducted for opioids, SSRIs, and sedative/anxiolytics, respectively. Several relevant effects were noted: (1) Pain evidenced strong associations with reduced functioning across both physical and psychosocial domains, (2) Opioid use held interactive relationships with PTSD across both functioning domains. Specifically, opioids were associated with greater physical impairment in patients without comorbid PTSD. Opioids also were related to greater psychosocial impairment in patients without PTSD while PTSD was associated with greater impairment in patients not using opioids, (3) Opioid use evidenced a marginal interaction with pain on psychosocial functioning. Opioids were associated with greater psychosocial impairment among patients with high-pain, and high-pain was associated with greater impairment among opioid users, (4) SSRIs held a marginal interaction with PTSD such that PTSD was related to poorer psychosocial functioning only among individuals not using an SSRI, and (5) Anxiolytic use evidenced a marginal interaction with PTSD on physical functioning although no between-group differences were noted. These data suggest that PTSD symptomology may be an important consideration in determining treatment modality for patients experiencing pain subsequent to traumatic injury.