Background: Melphalan hydrochloride is a primary agent used in the conditioning regimen for autologous stem cell transplant indications including multiple myeloma and lymphoma. Brand Alkeran labelling indicates the drug concentration must not exceed 0.45 mg/mL and should be given over a minimum 15 minutes but infused in its entirety within 60 minutes from preparation. Caution is provided as data has shown a loss of potency by 1% every 10 minutes after melphalan dilution. Time and concentration constraints often require the dose being divided into two infusion bags with the option to Y-site. These limitations necessitated an optimized process to ensure melphalan completion within the 60-minute timeframe. Methods: Our institution began to formally audit melphalan administration data in November 2018 as part of a new program quality metric. A retrospective evaluation was performed which assessed the total time from melphalan dilution in a normal saline (NS) bag to melphalan infusion completion. The aim was to increase compliance within 60 minutes from 86.2% to 100%. We utilized the Plan-Do-Study-Act (PDSA) cycle method to address opportunities for improvement. PDSA 1 included staff education on the importance of timely administration; same-day audit forms were created to dissect any potential fallouts promptly. This form included documentation of the time from vial reconstitution to delivery to the pharmacist within the patient care unit. Secondary to re-evaluation of package insert verbiage and discussion with the manufacturer, we redefined the audit start time to be melphalan vial reconstitution instead of dilution in the infusion bag. PDSA 2 incorporated specific checkpoints for vial reconstitution (12 minutes) and bag delivery (20 minutes) and changed from concurrent to sequential bag administration. Results: A total 285 melphalan infusions were eligible for analysis (mean 1.91 bags per patient). Baseline data showed 86.2% of infusions completed within the 60-minute timeframe. Average time-to-completion was 50.2 minutes (N=73). PDSA 1 revealed 100% compliance of chemotherapy verification documentation and 97.9% infusion completion with an average time of 42.8 minutes (N=97). PDSA 2 resulted 99.1% compliance (one infusion fallout) and an average completion time of 41.2 minutes (N=115). Overall survival (OS) at 1-year for baseline, PDSA 1, and PDSA 2 groups was 94.7%, 95.9%, and 98.3% respectively (p=0.66). Conclusions: The outcome measure average and mean time-to-completion improved from 86.2% to 99.1% and 50.2 to 41.2 minutes, respectively, secondary to process measure implementation despite the more stringent redefined vial dilution start time. A lone fallout of 62 minutes in PDSA 2 was triaged and determined to be due to unpredictable line complications. No significant differences in OS were observed. Ultimately, our process was optimized in terms of both compliance and efficiency.