A retrospective study of the clinical course and outcome of patients with serum digoxin concentrations (SDCs) greater than 3 ng/mL was conducted to determine the probability of a patient without initial signs or symptoms of digoxin toxicity subsequently developing signs or symptoms. Of 123 patients with SDCs greater than 3 ng/mL, 54 had no apparent signs or symptoms of toxicity at the time the index SDC was determined (group 1). Of these 54, two patients developed definite digoxin toxicity, although neither suffered significant morbidity. Digoxin administration was reduced or discontinued in all patients but one in group 1. There were no significant differences between the patients who had no signs or symptoms of digoxin toxicity (group 1) and those who did have signs or symptoms (group 2) in the mean SDC (3.9 ± 0.1 vs. 4.2 ± 0.2 ng/mL, respectively), the serum creatinine (2.9 ± 0.2 vs. 3.4 ± 0.4 mg/dL), or the incidence of atrial fibrillation (29/54 vs. 35/69) and coronary artery disease (21/54 vs. 18/69). The authors conclude that clinically stable patients receiving digoxin who have elevated SDCs but are without signs or symptoms of digoxin toxicity are at low risk of developing serious digoxin toxicity and do not generally require treatment beyond the discontinuation of digoxin therapy.