In an outpatient, home-use, random-order, controlled trial we compared automated glycemic control with the iLet bionic pancreas in the insulin-only (IOBP) vs. the bihormonal (BHBP) configurations for one week each in adult subjects (n=10) with type 1 diabetes. Subjects used their typical insulin analog (lispro or aspart) during both arms of the study. During the BHBP period the iLet delivered micro-doses of dasiglucagon, a glucagon analog stable in aqueous solution (Zealand Pharma). The insulin control algorithm was identical in both configurations, was initiated solely based on each subjects’ body mass without any information regarding patients’ baseline insulin needs, and used a glucose target of 110 mg/dl. The mean CGM glucose was lower in the BHBP arm vs. the IOBP arm (139±11 vs. 149±13 mg/dl, p=0.004) while the % of time with CGMG <54 mg/dl was nominally reduced (0.2%, IQR 0-0.4 vs. 0.6%, IQR 0.2-1.1%, p=0.11). We used an autoregressive time series model to determine statistical significance for differences between arms for each individual subject. Eight subjects had a significantly lower mean CGMG during the BHBP arm (p<0.05, mean improvement 12±7 mg/dl), while in the remaining two subjects there was no significant difference (nominal absolute difference 2±1 mg/dl). Eight of the ten subjects had a nominal reduction of the % of time <54 mg/dL in the BHBP arm (mean nominal difference -0.5%, range -0.1 to -1.0%), none of which were statistically significant. Here we demonstrated significant benefit of adding dasiglucagon in eight of ten subjects, allowing them to achieve a lower mean glucose without increased rates of hypoglycemia, in a trial comparing the BHBP and IOBP configurations of the iLet. Disclosure J. Sherwood: None. C.A. Balliro: None. R.Z. Jafri: None. L.E. Castellanos: None. M. Hillard: None. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. E. Greaux: None. H. Zheng: None. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care. Funding Beta Bionics, Inc.