Background: Hospital pharmacists make many recommendations that improve patients' quality of care and/or reduce drug costs. While the impact of quality-of-care interventions is difficult to quantify, those limited to cost savings could be assessed in a prospective, randomized fashion. Objective: To assess the impact of pharmacist-initiated interventions on cost savings. Methods: Six pharmacists at a large university hospital recorded patient- specific recommendations for 30 days. All quality-of-care interventions were completed by the pharmacists, but those strictly aimed at reducing costs were stratified by drug class and randomized to an intervention or control group. Pharmacists contacted physicians with cost-saving recommendations in the intervention group, while control group patients were simply observed. Main Outcome Measure: Drug costs after randomization. Results: Most (n=967 [79%]) of the 1226 interventions recorded were aimed at improving quality of care. The remaining 259 (21%) provided equivalent quality of care, but at less expense. These cost-saving interventions typically involved streamlining therapy to less expensive agents (39%), discontinuing an unnecessary medication (25%), or modifying the route of administration (24%). The group randomized to receive a pharmacist's intervention had drug costs that were 41% lower than those in the control group (mean, $73.75 vs $43.40; P<.001). Interventions involving anti-infective agents had the greatest cost savings (mean, $104.08 vs $58.45; P<.001). For our institution, this extrapolates to an annual savings of approximately $394 000 (95% confidence interval, $46 000-$742 000). As expected, these interventions had no impact on length of hospital stay, inhospital mortality, 30-day readmissions, or the need to readminister the targeted medication or restart intravenous therapy. Conclusions: While interventions solely aimed at reducing costs represent a small portion of a pharmacist's activities, they can result in significant savings for an institution.