Background: The addition of olanzapine to high emetic risk chemotherapy regimens substantially improves nausea and vomiting within 24 hours and is recommended in the guidelines of both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN). However, the uptake of olanzapine has been low in national and institutional settings. The purpose of this project was to increase guideline-concordant prescribing of olanzapine in eligible patients in a community oncology practice. Methods: We developed a multiphase program to address the barriers to the use of olanzapine in a community oncology practice. Patients’ medical records (N = 423) were reviewed to collect baseline data. Motivational interviewing with prescribing clinicians elicited barriers to prescribing, reinforced clinical guidelines, and elicited and reinforced language that suggested a willingness to change prescribing patterns. Chemotherapy protocols were subsequently updated to include olanzapine for high emetic chemotherapy regimens, and prescriber and nurse education was provided by our pharmacists regarding the most recent ASCO and NCCN guidelines. A fellow-led educational session was provided to the infusion nursing team and care managers. At the end of a seven-month period, prescribing information was identified through a system-generated report followed by a medical record review for validation (N = 136) and was shared monthly with prescribing clinicians. Results: At baseline, the use of olanzapine was zero. Multiple barriers were identified regarding the use of olanzapine during motivational interviewing with clinicians, including lack of knowledge of the guidelines, belief that most patients do not require olanzapine, concerns about sedation with the previously recommended dose of 10 mg, and order sets that did not include olanzapine. After the interventions, there was a statistically significant increase in the use of olanzapine from 0% to 56% (p-value < 0.001). Conclusions: A combination of motivational interviewing, prescriber and nurse information support, and changes to the pre-populated order sets for chemotherapy antiemetics was highly successful in improving the uptake of guideline-concordant prescribing of antiemetics. This model of quality improvement, including motivation interview, may support quality improvement efforts across oncology.