OBJECTIVES: Economic evaluation is increasing common in clinical trials. Often, individuals' health care costs are not observed in these trials, rather health care cost estimates are often calculated from observed resource use and unit prices estimated from other sources. The level of detail collected in clinical trials varies and determines which resource costing methods can be used. Using hospital inpatient data, this study compares three resource costing methodologies that utilize varying levels of information about hospitalizations. METHODS: As part of project TrEAT, an alcohol-related intervention study, hospital primary discharge data were collected for HMO patients. Data from HCUP National Inpatient Sample (NIS) 2000 are used for estimating unit prices. Three resource costing methods are applied: 1) a per day unit price over all hospitalizations; 2) a unit price per day for each DRG; and 3) a unit price per day for each primary ICD-9-CM discharge diagnosis. Inpatient costs are calculated as the product of these unit prices and the observed inpatient days. Inpatient costs for the intervention and control groups are compared. RESULTS: For the 1-year period following study enrollment, method 1 yields control and intervention group averages of $485($2736) and $246($1458), respectively. Method 2 produced mean and standard deviations of costs that were approximately twice as large, $956($5695) and $543($3755) for the control and intervention group, respectively. Method 3 produced mean and standard deviations larger than Method 1 but smaller than Method 2: $691($3740) and $445($2982) for the control and intervention group, respectively. Differences between the intervention arms are greater using Method 2, ($412 versus $238 and $245). CONCLUSIONS: The level of resource use detail can affect the results of economic evaluation of clinical trials. Costing hospitalizations using DRG level data resulted in larger differences between intervention arms than methods using ICD-9-CM level data or a fixed per diem amount.