Vancomycin is often initiated in hospitalized patients; however, it may be unnecessary or continued for longer durations than needed. Oversight of all vancomycin orders may not be feasible with widespread prescribing and strategies to enlist other clinicians to serve as stewards of vancomycin use are needed. We implemented 2 sequential interventions: a protocol in which the pharmacist orders MRSA nasal swab followed by a protocol requiring approval from pharmacists to continue vancomycin for >72 hours. In this single-center, retrospective, quasi-experimental study, we evaluated vancomycin use after implementation of a pharmacy-driven MRSA nasal-swab ordering protocol and a vancomycin 72-hour restriction protocol. The primary outcome was the change in the standardized antibiotic administration ratio (SAAR) for antibacterial agents for resistant gram-positive infections. We also evaluated the impact on antibiotic utilization. Following the MRSA swab protocol, the SAAR decreased from 1.26 to 1.13 (P < .001; 95% confidence interval [CI], 1.16-1.25). After the 72-hour approval process, the SAAR was 0.96 (P < .001; 95% CI, 1.0-1.12). Vancomycin utilization decreased from 138.9 to 125.3 days of therapy per 1,000 patient days following the MRSA swab protocol (P < .001) and to 112.7 (P < .001) following the 72-hour approval protocol. Interrupted time-series analysis identified a similar rate of decline in utilization following the 2 interventions (-0.3 and -0.5; P = .16). Both interventions combined resulted in a significant reduction (-1.5; P < .001). Implementation of a pharmacist-driven MRSA nasal-swab ordering protocol, followed by a 72-hour approval protocol, was associated with a significant reduction in the SAAR for antibiotics used in the treatment of resistant gram-positive infections and a reduction in vancomycin utilization. Leveraging the oversight of primary service clinical pharmacists through these protocols proved to be an effective strategy.