In a random-order, outpatient crossover trial we compared automated glycemic control with the insulin-only bionic pancreas (BP) to usual care in subjects with T1D. Subjects transitioned directly to the BP from CSII or MDI (insulins glargine n=6, detemir n=1, or degludec n=5). The BP continuously adapts to individual insulin needs and was initialized based on body mass only, without information about the baseline insulin regimen. The first 24 hours of BP control was compared to days 3-7 (the 5-day period considered for the primary outcome) to examine the effect of having received long-acting insulin the day prior to initiation of the BP. As shown in the Table, the mean CGM glucose and time-in-range did not differ between the first 24 hours and days 3-7 after starting the BP in subjects on MDI at baseline, while there was a reduction in mean and an increase in time-in-range among those on CSII at baseline. Subjects on MDI at baseline did not experience more hypoglycemia in the first 24 hours despite having long-acting insulin on board. Both subjects on MDI and CSII at baseline achieved good glucose control on the BP (see Table). Surprisingly, there was no difference in the insulin total daily dose (TDD) between the first 24 hours and days 3-7 in the MDI users despite an average TDD of basal insulin at baseline of 15 u/day. These results suggest that BP therapy can be safely initiated directly from MDI regimens. Disclosure J. Sherwood: None. C.A. Balliro: None. F. El-Khatib: Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. L. Ekhlaspour: None. L. Hsu: None. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care. E. Damiano: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Beta Bionics. Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. Stock/Shareholder; Spouse/Partner; Beta Bionics. Other Relationship; Self; Ascensia Diabetes Care, Senseonics. S.J. Russell: Advisory Panel; Self; Companion Medical, Unomedical a/s. Consultant; Self; Flexion Therapeutics. Research Support; Self; Beta Bionics, MITRE Corporation, Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Self; ADOCIA, Ascensia Diabetes Care, Ascensia Diabetes Care, Lilly Diabetes, Roche Diabetes Care, Senseonics. Funding National Institutes of Health (NIDDKUC4DK108612)