Abstract Background The advent of medical therapies for congestive heart failure that have proven survival benefits, specifically angiotensin-converting enzyme (ACE) inhibitors, β-adrenergic antagonists, and the aldosterone antagonists, have called into question the use of digoxin for patients with normal sinus rhythm, left ventricular dysfunction, and symptomatic heart failure. This issue appears to have been heightened after the publication of the results of the Digitalis Investigation Group (DIG) Trial in 1997 that did not demonstrate a statistically significant impact of digoxin on mortality. Methods and Results We used data from a large heart failure registry to examine digoxin use at the time of hospital admission for heart failure, a surveillance system for recording toxic drug exposures to describe patterns in digoxin toxicity and industry estimates for the use of digoxin antibody. Digoxin use has decreased significantly from 31.4% in late 2001 to 23.5% in late 2004 ( P < .00001) independent of patient age, gender, or baseline creatinine. Conversely, the number of toxic or potentially toxic exposures to digoxin requiring hospitalization has not decreased. Conclusion Digoxin use is decreasing but there has not been a similar decline in cases of toxicity. Further analyses are required to delineate the reasons underlying these trends and the appropriateness of prescribing practices for both digoxin and its antidote.