We examined automated glycemic control with the insulin-only configuration of the iLet® bionic pancreas using faster aspart (Fiasp), comparing non-default tmax settings of the iLet® to a default tmax setting in a two-period, random-order cross-over design within each of three cohorts with eight different participants. Each participant was randomized to use the default tmax setting (t65 minutes) followed by the non-default tmax setting (t50, t40, or t30 minutes in cohorts 1, 2, and 3, respectively), or vice versa, for one week each. The group mean CGM glucose (CGMG) was significantly lower (two-sided p-value <0.05) in the t50 versus t65 arm (-7.4 [-12.3; -2.4] mg/dl, p=0.011; 150.3 versus 157.7 mg/dl) and in the t40 versus t65 arm (-7.5 [-12.9; -2.1] mg/dl, p=0.015; 150.1 versus 157.6 mg/dl), but was not significantly different in the t30 versus t65 arm (-7.7 [-16.8; 1.4] mg/dl, 144.2 versus 151.9 mg/dl). Group mean time <54 mg/dl was not significantly different between non-default and default tmax settings in all three cohorts, (+0.09%, +0.18%, and +0.17% in cohorts 1, 2, and 3, respectively, all p>0.05). Using an autoregressive time series model, we determined the intra-individual statistical significance of differences in mean CGMG and time <54 mg/dl between non-default and default tmax settings. The mean CGMG was significantly different for four of eight subjects in the t50 versus t65 cohort (mean -13±7 mg/dl), seven of eight subjects in the t40 versus t65 cohort (mean -8±8 mg/dl), and five of eight subjects in the t30 versus t65 cohort (mean -12±6 mg/dl). One subject had a significant change in time <54 mg/dl (+1.2% of time; 1.2% versus 0%) in the t40 versus t65 arm. The majority of subjects had a significant reduction in mean CGMG with a non-default tmax setting while using Fiasp in the iLet. Use of different tmax settings could translate to clinically significant reductions in mean CGMG for many patients, with low risk of a significant increase in hypoglycemia. Disclosure L.E. Castellanos: None. H. Zheng: None. C.A. Balliro: None. J. Sherwood: None. M. Ekelund: Employee; Self; Novo Nordisk. Stock/Shareholder; Self; Novo Nordisk. Stock/Shareholder; Spouse/Partner; Novo Nordisk. 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.