Medical patients receiving IV therapy were randomly assigned to one of two IV tubing change groups. One group had a 48-hour tubing change and the other had no tubing change for the remainder of the cannula placement. A daily IV fluid specimen was processed microbiologically. To complete the study, a minimum of 3 continuous days of therapy and three fluid specimens was required. There were two contaminated specimens, one in each tubing change group. The contamination rate in the 48-hour change group was 0.87% and 0.96% in the no change group. The rate difference of 0.09% has a 95% confidence interval (−0.035 to +0.036) which includes zero. Survival analysis also revealed no significant difference in the cumulative probability of survival, however the mean duration of continuous tubing use of 4.3 days in the no change group and 1.8 days in the 48 hour change group were significantly different (p<0.05). The cumulative probability of surviving contamination free was 0.988 in the 48-hour group and 0.987 in the no-change group. We conclude that it is safe to change IV tubing at intervals up to but not exceeding 4 days.