No studies testing the safety of changing intravenous systems containing in-line burettes at 72 hours in an intensive care setting have been performed. Patients entering a medical or surgical intensive care unit were alternatively assigned to have any line with an in-line burette changed at either 48 hour (105 patients) or 72 hour (65 patients) intervals. Daily quantitative cultures with a 2 ml aliquot of burette fluid were obtained. Contaminated burette fluid was detected in 60 of 1181 (5.0%, 95% confidence interval, 3.7% to 6.3%) samples from the burettes changed at 48 hour intervals, and in 40 of 901 (4.4%, 95% confidence interval, 3.0% to 5.8%) samples from 72 hour interval burettes. Significant bacterial contamination of burette fluid, defined as ten or more colonies per milliliter, occurred in only seven (0.6%) cultures from patients in the 48 hour interval group compared with only three (0.3%) cultures in the 72 hour group. None of the contaminated burette fluids was associated with a primary bacteremia. Change of in-line burettes in patients in intensive care at 72-hour intervals is safe and should result in substantial cost savings to hospitals.