OBJECTIVES: To measure relative rates of discontinuation among commonly prescribed chronic disease medication classes under conditions of routine care. METHODS: De-identified pharmacy records for 1.99 million patients who received medication from retail pharmacy chains throughout the United States were used to select patients who obtained a fill between January 1, 2007 and January 30, 2007 for any of the following medication classes: antidepressants (n=339,059); bisphosphonates (n=120,098); cardiovascular agents (n=622,947); glaucoma medications (n=48,229); statins (n=452,978); inhaled steroids (n=95,900); insulins (n=66,637); and oral antidiabetic agents (n=248,280). The primary outcome measure was the median time-to-discontinuation (TD50). Kaplan-Meier analysis was used to estimate the risk of discontinuation over the subsequent 360 days for both “inexperienced” and “experienced” groups of patients. Inexperienced patients were defined as those who had not been dispensed an in-class medication in the prior 180 days; experienced patients were those who had been. Discontinuation was defined as being 30 days late for a scheduled refill. Patients switched to an in-class medication were considered to have continued therapy. RESULTS: Median days to discontinuation (TD50) among patients who had not filled a prescription for an in-class medication in the prior 180 days were: inhaled steroids (TD50=30); insulins (TD50=45); antidepressants (TD50=67); bisphosphonates (TD50=82); cardiovascular agents (TD50=85); statins (TD50=90); oral antidiabetic agents (TD50=90); and glaucoma medications (TD50=120). Rates of medication discontinuation among patients who had filled a prescription for an in-class medication in the prior 180 days were: inhaled steroids (TD50=60); insulins (TD50=130); glaucoma medications (TD50=180); antidepressants (TD50=187); cardiovascular agents (TD50=240); oral antidiabetic agents (TD50=270); bisphosphonates (TD50=272); and statins (TD50=308). CONCLUSIONS: Patients new to therapy faced a far higher likelihood of medication discontinuation compared to those with prior in-class medication experience among all the medication classes studied. Providers and health care systems may want to re-engineer care to provide more frequent follow-up and education to this commonly treated, high-risk group.