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Objective To determine what triggers the use of digoxin therapeutic drug monitoring (TDM) that adheres to established indications and the change in digoxin dosage after the result of monitoring is obtained. Methods This prospective study included 86 patients admitted to 6 medicine wards and 2 intensive cardiac care unit wards in a tertiary-care center. Data on patients' demographics, drug therapy, serum chemistry values, indications for digoxin therapy, indications for ordering the drug assay, timing of the blood sample relative to administration of the last dose, and physicians' decisions after attaining serum digoxin concentrations were collected. Results Eighty-six digoxin assays were evaluated. Indications for the use of a digoxin assay were mostly routine without a clear indication (66%); in only 22% of the assays were orders considered clinically justified. Eleven patients had concentrations >2 ng/mL, but only 8 patients had digoxin intoxication. In only 31% of patients did the medical staff respond to the results. In only 21% of patients with subtherapeutic drug concentrations was there a change in digoxin dose. Conclusions Although there are clear indications for the use of digoxin TDM, physicians seem to routinely order these blood tests. The clinicians did not adequately use the digoxin concentration data to optimize therapy. The assistance of a clinical pharmacist or pharmacologist is warranted for use of the assays, to optimize digoxin therapy.