Previous research has shown that a small proportion of the population accounts for a substantial proportion of spending on physician and hospital services. Much less is known about the high-cost users of ambulatory prescription medicines. We investigate the concentration and sustained nature of ambulatory prescription drug expenditures among residents of British Columbia, Canada in 2001 and 2004. Linking person-specific administrative data from several sources, we examine the demographics, socio-economic status, and health status of high-cost ambulatory pharmaceutical users and the extent that high-cost pharmaceutical use was sustained, at the individual level, from 2001 to 2004. The top 5% of users were responsible for 48% of ambulatory prescription expenditures in the province. A significant burden of morbidity, as well as sustained high expenditures, characterized these users. They were older, more likely to be female, more likely to be of low income, and more likely to be hospitalized and die within the year of study than other pharmaceutical users and non-users. Our results suggest that careful consideration should be given to the long-term financial burdens and access barriers created by pharmaceutical insurance policies that rely heavily on private payments by individuals. Our focus is on costs associated with ambulatory prescription drug use, however, had we included information on the cost of prescription drugs used in hospitals, we would likely have detected an even stronger relationship between high-cost pharmaceutical use and poor health status.