Background: Despite improved survival and increasing hospital mandates, discordance with sepsis resuscitation guidelines is common. We sought to determine whether choice architecture can promote faster or slower decision-making among physicians and the associated risk of guideline-discordance in sepsis.Methods: We conducted an electronic, survey-based time-to-event analysis using a sepsis clinical vignette and multivariable Cox proportional hazards regression. Respondents included physicians from multiple specialties and levels of training at an academic tertiary-care hospital and academic safety-net hospital. Respondents were randomized to one of three distinct answer sets: control (6 options with no time limit), time constraint (10 seconds, intended to promote faster thinking) or choice overload (24 options, intended to promote slower thinking). The primary outcomes were response time and discordance with Surviving Sepsis Campaign 2016 fluid resuscitation guidelines, adjusting for physician characteristics. Physician risk tolerance and predisposition towards intuitive or analytical thinking were assessed for effect modification.Results: 189 of 624 (30.3%) physicians completed the survey. Total response time was lower in time constraint (45.8s, IQR 38.3s-56.6s, P<0.001) and higher in choice overload (94.2s, IQR 73.0s-142.6s, P=0.005) groups compared to control (71.5s, IQR 52.6s-100.6s). In contrast, relative hazard for guideline discordance was increased in time constraint (3.38, 1.97-5.79, P<0.001) and decreased in choice overload (0.52, 0.30-0.93, P=0.03) groups dependent on Cognitive Reflection Test (7.87, 1.80-34.44, P=0.006) and risk tolerance scores (JPI-RTS 2.00, 1.05-3.84, P=0.04 and MFS 0.42, 0.20-0.88, P=0.02), respectively.Conclusions: Choice architecture may impact clinical decisions and guideline discordance in sepsis, warranting further investigation in real-world contexts.