To determine the clinical and financial outcomes of antibiotic practice guidelines implemented through computer-assisted decision support. Descriptive epidemiologic study and financial analysis. 520-bed community teaching hospital in Salt Lake City, Utah. All 162 196 patients discharged from LDS Hospital between 1 January 1988 and 31 December 1994. An antibiotic management program that used local clinician-derived consensus guidelines embedded in computer-assisted decision support programs. Prescribing guidelines were developed for inpatient prophylactic, empiric, and therapeutic uses of antibiotics. Measures of antibiotic use included timing of preoperative antibiotic administration and duration of postoperative antibiotic use. Clinical outcomes included rates of adverse drug events, patterns of antimicrobial resistance, mortality, and length of hospital stay. Financial and use outcomes were expressed as yearly expenditures for antibiotics and defined daily doses per 100 occupied bed-days. During the 7-year study period, 63 759 hospitalized patients (39.3%) received antibiotics. The proportion of the hospitalized patients who received antibiotics increased each year, from 31.8% in 1988 to 53.1% in 1994. Use of broad-spectrum antibiotics increased from 24% of all antibiotic use in 1988 to 47% in 1994. The annual Medicare case-mix index increased from 1.7481 in 1988 to 2.0520 in 1993. Total acquisition costs of antibiotics (adjusted for inflation) decreased from 24.8% ($987,547) of the pharmacy drug expenditure budget in 1988 to 12.9% ($612,500) in 1994. Antibiotic costs per treated patient (adjusted for inflation) decreased from $122.66 per patient in 1988 to $51.90 per patient in 1994. Analysis using a standardized method (defined daily doses) to compare antibiotic use showed that antibiotic use decreased by 22.8% overall. Measures of antibiotic use and clinical outcomes improved during the study period. The percentage of patients having surgery who received appropriately timed preoperative antibiotics increased from 40% in 1988 to 99.1% in 1994. The average number of antibiotic doses administered for surgical prophylaxis was reduced from 19 doses in the base year to 5.3 doses in 1994. Antibiotic-associated adverse drug events decreased by 30%. During the study, antimicrobial resistance patterns were stable, and length of stay remained the same. Mortality rates decreased from 3.65% in 1988 to 2.65% in 1994 (P < 0.001). Computer-assisted decision support programs that use local clinician-derived practice guidelines can improve antibiotic use, reduce associated costs, and stabilize the emergence of antibiotic-resistant pathogens.