Purpose: Vancomycin prescribing requires individualized dosing and monitoring to ensure efficacy, limit toxicity, and minimize resistance. Although there are nationally endorsed guidelines from several countries addressing the complexities of vancomycin dosing and monitoring, there is limited consideration of how to implement these recommendations effectively. Methods: We conducted a systematic search of multiple databases to identify relevant comparative studies describing the impact of interventions of educational meetings, implementation of guidelines, and dissemination of educational material on vancomycin dosing, monitoring, and nephrotoxicity. Effect size was assessed using ORs and pooled data analyzed using forest plots to provide overall effect measures. Results: Six studies were included. All studies included educational meetings. Two studies used implementation of guidance, educational meetings, and dissemination of educational materials, one used guidance and educational meetings, one educational meetings and dissemination of educational materials, and two used educational meetings solely. Effect sizes for individual studies were more likely to be significant for multifaceted interventions. In meta-analysis, the overall effect of interventions on outcome measures of vancomycin dosing was OR 2.50 (95% CI 1.29–4.84); P< 0.01. A higher proportion of sampling at steady-state concentration was seen following intervention (OR 1.95, 95% CI 1.26–3.02; P<0.01). Interventions had no effect on appropriate timing of trough sample (OR 2.02, 95% CI 0.72–5.72; P=0.18), attaining target concentration in patients (OR 1.50, 95% CI 0.49–4.63; P=0.48, or nephrotoxicity (OR 0.75, 95% CI 0.42–1.34; P=0.33). Conclusion: Multifaceted interventions are effective overall in improving the complex task of dosing vancomycin, as well as some vancomycin-monitoring outcome measures. However, the resulting impact of these interventions on efficacy and toxicity requires further investigation. These findings may be helpful to those charged with designing implementation strategies for vancomycin guidelines or complex prescribing processes in hospitals.