The economic and clinical outcomes of a pharmacist-managed proactive program that used predetermined clinical criteria for converting levofloxacin therapy from i.v. to oral without physician approval were examined. A prospective observational study (POS) assessing the standard of care was conducted over two months and was compared with a proactive conversion program (PCP). A cost-minimization analysis was performed from the provider's perspective. The analysis was divided into cost levels 1, 2, and 3. During the POS and PCP, 49 and 82 patients were evaluated, respectively. The percentage of patients meeting conversion criteria in each group was similar (61% POS versus 65% PCP) (p = 0.827). Candidates met criteria for conversion on day 2 in both groups. The average days that conversion occurred during the POS and PCP were days 7 and 3, respectively (p = 0.010). In those patients, the length of stay was significantly shorter for the PCP (6 versus 9.5 days) (p = 0.031). Level-1, level-2, and level-3 costs were significantly less during the PCP than during the POS for patients who met conversion criteria ($77 versus $133, $91 versus $151, and $13,931 versus $17,198, respectively). Two patients in the PCP were switched back to i.v. levofloxacin due to noninfection-related complications. The overall clinical success rate for evaluable conversion candidates was 100% during the PCP. A pharmacist-managed proactive program that used predetermined clinical criteria for converting levofloxacin therapy from i.v. to p.o. without physician approval reduced length of stay and institutional health care costs without compromising clinical outcomes.