The objective of this study, conducted at Hospital Clínico San Carlos, Madrid, Spain, was to compare the cost of treatment of Gram-positive infections with teicoplanin and vancomycin under normal conditions. Using a prospective observational study design for drug utilization and economic assessment, we evaluated the comparability of the sample, adverse events, features of treatment with teicoplanin/vancomycin and factors influencing the consumption of resources until the end of glycopeptide treatment or discharge (whichever occurred later) using Health System perspective. Costs were assigned using the hospital's evaluation at the time of the study. Analyses made: multivariate, sensitivity (by modifying staff or acquisition costs) and simulation of reduction of stay by early discharge in the teicoplanin group. Study participants included 201 patients who had been using teicoplanin (n=100) or vancomycin (n=101) for at least four days. Data collected daily outside morning work timetable. Costs of acquisition, administration and monitoring by course of treatment (mean+/-SD, in euros) were lower in the vancomycin group (teicoplanin euro647.62+/-euro572.75 vs. vancomycin euro378.11+/-euro225.90); when total costs (including hospital stay) were considered, no differences were found (teicoplanin euro4,432.04+/-euro3,383.46 vs. vancomycin euro4,364.44+/-euro2,734.24). Conditions of use and results were similar for both antibiotics. The economic results of acquisition, administration and monitoring were advantageous for vancomycin; when global costs of care were taken into account, these differences were not evident. Tolerability was significantly advantageous in the teicoplanin group (with regard to phlebitis and elevation of creatininemia), without differences in clinical or economic outcomes. The formulation of teicoplanin did not take advantage of its potential benefits of administration.