A population base of 6,367 in-patients from 28 general hospital wards was included in a nation-wide project aimed at documenting the extension and criteria of therapeutic drug monitoring (TDM). On randomly selected index days over a 3-month period details of age, clinical status, renal and liver function, diseases, drug therapies, and drug monitoring of all in-patients of eight different clinical specialties were recorded and analyzed. A total of 648 requests for 387 patients (16.3% of the population given drugs for which TDM was available in the hospital) was traced. Digoxin was the most frequently monitored drug (481 requests for 289 patients), accounting for 74% of the overall requests. This finding is consistent with the yearly activity of the laboratories of the same hospitals, which documented that 63% of the whole in-hospital analytical work (29,396 out of 46,692 requests) concerned digoxin. From a more qualitative point of view, data are provided that document a largely inappropriate use of TDM, which was employed only for 20% of patients who might have benefited from it.