Objective To examine variation in pharmaceutical spending and patient characteristics across prescription drug user groups. Data Sources British Columbia's population‐based linked administrative health and sociodemographic databases (N = 3,460,763). Study Design We classified individuals into empirically derived prescription drug user groups based on pharmaceutical spending patterns outside hospitals from 2007 to 2011. We examined variation in patient characteristics, mortality, and health services usage and applied hierarchical clustering to determine patterns of concurrent drug use identifying high‐cost patients. Principal Findings Approximately 1 in 20 British Columbians had persistently high prescription costs for 5 consecutive years, accounting for 42 percent of 2011 province‐wide pharmaceutical spending. Less than 1 percent of the population experienced discrete episodes of high prescription costs; an additional 2.8 percent transitioned to or from high‐cost episodes of unknown duration. Persistent high‐cost users were more likely to concurrently use multiple chronic medications; episodic and transitory users spent more on specialized medicines, including outpatient cancer drugs. Cluster analyses revealed heterogeneity in concurrent medicine use within high‐cost groups. Conclusions Whether low, moderate, or high, costs of prescription drugs for most individuals are persistent over time. Policies controlling high‐cost use should focus on reducing polypharmacy and encouraging price competition in drug classes used by ordinary and high‐cost users alike.