OBJECTIVES: Evaluate the useffulness of cost per DDD to identify problematic drugs in medium- and high-level complexity hospitals from Colombia. METHODS: This was a cross-sectional study where drug prescriptions were evaluated in 331 second- and third-level complexity hospitals from 27 Colombian departments during 2006-2007. RESULTS: A total of 38,863 prescriptions for 3663 patients were analyzed; 54.7% of them patients affiliated to contributory health care system. The medication consumption was of 8, 39 daily defined doses (DDD)/1000 patients. Filgastrim and Interferon represent almost 48% of DDDs of DU90%. The overall cost per DDD was US$3.9, being this cost lower in drugs of DU90% than drug out of this list (US$1.79 vs.US$10.24, p=0.03). Also the cost per DDD was higher in patients affiliated to contributory health care system than patients affiliated to public health care system (US$ 3.01 vs. US$2.09, p=0.03). The antineoplastic and immunomodulating agents (Code L, ATC Classification System), and drugs of musculoskeletal system (Code M, ATC Classification System) were the drugs with higher cost per DDD (US$ 1686 and US$8.9, respectively). CONCLUSIONS: In this population, antineoplastic and immunomodulating agents have cost per DDD that were 100 times higher than other drugs , also the estimation of cost per DDD allows identifying problematic drugs in this population such as Filgastrim and Interferon which prescriptions must be check carefully. Were evident differences of drug´s cost by type of health care system regardless that do not exist differences of drugs coverage in the Colombian health system by affiliation. The cost per DDD and DU 90% are useful indicators to identify problematic drugs in developing countries