Overutilization of intravenous (IV) medications can result in drug shortages, which is one of the major health care crisis, in addition to increasing costs, length of hospital stays (LOS) and the associated complications. We hypothesized that IV therapy was overused at our hospital where oral (PO) was applicable, and that the implementation of IV-PO protocol could result in a cost-effective practice. Hence, we aimed at assessing impact and outcomes of implementing such a protocol. A single center, prospective quasi-interventional study conducted at tertiary academic hospital. A protocol was implemented targeting 17 medications, with educational sessions to medical staff during a 5-month phase. IV orders of 48 h or more, among adult patients at medical or surgical wards with no contraindication to PO route were eligible. Once eligible, pharmacists send interventions using hospital’s computerized order entry system, and physicians’ responses were monitored on daily basis. Efficacy was estimated by percentage of switch recommendations that resulted in effective switch to PO medication. Cost-minimization analysis was used for course cost between the control phase and intervention phase. Length of hospital stay (LOS), readmissions within 90 days and in-hospital mortality were analyzed as secondary outcomes. During intervention phase, 781 patients had at least one IV order switched to PO. Gastric acid-reducing agents (GARAs) accounted for the most IV prescriptions (50.4%), followed by antibiotics (39.6%). Pharmacists carried out 2677 interventions to which switch recommendations were issued in 1185 (44.3%). Primary switch recommendations (N = 677) led to effective switch in 60.7% cases. These included per protocol switch (8.9%), switch to another PO (2.5%), spontaneous switch by physician (17.6%) and IV discontinuation (31.8%). The overall efficacy was estimated as 62.8%. The intervention was associated with reduced IV consumption from 4,574–18,597 vials in control phase to 3,654–15,546 vials in intervention phase, which resulted in overall cost saving of 50,960.8 SAR ($13,589.5), with an average monthly cost saving of 10,192.2 SAR ($2,717.9). Pharmacist-managed early switch from IV-PO therapy, with physicians’ education, showed significant reduction in IV medication use in our hospital. By reducing unnecessary IV use, this strategy enabled considerable cost savings, besides the potential advantages of convenience and safety.