Potentially preventable adverse drug-drug interactions increase morbidity and financial costs to hospitals and third party payers. This study's purpose is to document the prevalence of potential drug-drug interactions (PDDI) in patients referred to a Physical Medicine and Rehabilitation (PM&R) clinic, to identify risk factors associated with PDDI, and to evaluate physicians' ability to correctly identify these PDDI. Current medication lists were obtained by questionnaire and confirmed by chart review for 121 consecutive new patients. The physician-identified PDDI were compared with computer-identified PDDI. Twenty-seven patients (22%; 95% confidence interval, 15-31%) had PDDI. PDDI were associated with number of medications (P = 0.0011) and PM&R subspecialty clinic (P = 0.012). Twenty-nine of the 46 computer-identified interactions (63%) were not identified by the physicians, and the physicians falsely identified 28 other drug combinations as PDDI. Potential drug-drug interactions occur at high rates in PM&R outpatient populations, and physicians are inadequately prepared to identify these PDDI.