Reports of adverse events often surface shortly after a new drug is introduced, and in many cases provoke governmental regulatory action. Deaths pose a particular challenge, because drug takers may have excess mortality risk relative to nontakers for reasons unrelated to drug use. Aside from the implications for safety surveillance, a spurious association between drug use and mortality also can confound economic comparisons based on drug use. OBJECTIVES: To investigate, at the request of the U.K. Medicines Control Agency, safety and health-care resource utilization related to use of a new drug. METHODS: A postmarketing surveillance program was implemented at major medical schools in England and Scotland to monitor mortality, morbidity, and health-care resource utilization associated with use of a new drug for treating gastrointestinal conditions. The study employs a longitudinal design that identified 18,000 drug takers through automated pharmacy listings at 700+ general practitioner offices located within a one-hour drive from the medical schools. In addition to drug taking patterns and adverse event occurrences, use of ambulatory and hospital health-care resources are recorded. Instead of employing a reference group of nontakers, national death rates will serve as "historical controls." RESULTS: Morbidity and mortality experience among drug takers will be assessed by reviewing whether incidents occurred concomitantly with use of the medicine, by examining relationships with dose and duration of use, and other evidence to establish "biologic plausibility." These experiences will be related in turn to selected measures of health-care resource utilization. CONCLUSION: This study provides a useful template for future research to establish the safety and healthcare resource utilization profiles of a new drug.