Beta blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are evidence-based medications for chronic heart failure, but little is known about the persistent use and clinical effectiveness of these medications. We evaluated the longer-term use of β blockers and ACEIs/ARBs in patients with left ventricular systolic dysfunction and coronary artery disease. Patients with an ejection fraction <40% and coronary artery disease who had a cardiac catheterization from April 1994 through December 2005 were identified. Long-term patterns of β-blocker and ACEI/ARB use were categorized as persistent, new, previous, or no use based on information from routine follow-up surveys. Characteristics among medication-use groups were explored, and survival associated with persistent use was determined. Of 3,187 patients identified for the β-blocker analysis, 1,339 (42.0%) had persistent use. Conditional on surviving for ≥2 follow-up surveys, the adjusted risk of death was statistically significantly lower with persistent use versus no use (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.65 to 0.82) and new use versus no use (HR 0.81, 95% CI 0.68 to 0.97). Adjusted risk of death was not statistically significantly different between persistent or new use of an evidence-based β blocker and persistent use of a nonevidence-based β blocker (HR 0.96, 95% CI 0.78 to 1.17). Of 3,166 patients identified for the ACEI/ARB analysis, 1,347 (42.5%) had persistent use. There was no statistically significant association between adjusted mortality and persistent use (HR 0.93, 95% CI 0.81 to 1.05), new use (HR 0.86, 95% CI 0.71 to 1.03), or previous use (HR 0.88, 95% CI 0.73 to 1.07) compared with no ACEI/ARB use. In conclusion, persistent and new use of β blockers was associated with survival, but evidence-based β blockers did not appear superior to nonevidence-based β blockers. We were unable to demonstrate a statistically significant association between persistent ACEI/ARB use and survival.