Background: The optimal adjuvant vasopressor to norepinephrine in septic shock remains controversial. Objective: To compare durations of shock-free survival between adjuvant vasopressin and epinephrine. Methods: A retrospective, single-center, matched cohort study of adults with septic shock refractory to norepinephrine was conducted. Patients receiving norepinephrine not at target mean arterial pressure (MAP; 65 mm Hg) were initiated on vasopressin or epinephrine to raise MAP to target. Vasopressin-exposed patients were matched to epinephrine-exposed patients using propensity scores. Mortality outcomes were examined using multivariable Poisson regression with robust variance estimation. Results: Of 166 patients, 96 (entire cohort) were included in the propensity score–matched cohort. Shock-free survival durations in the first 7 days were similar between epinephrine- and vasopressin-exposed patients in the matched cohort (median = 13.2 hours, interquartile range [IQR] = 0-121.0, vs median = 41.3 hours, IQR = 0-125.9; P = 0.51). Seven- and 28-day mortality rates were similar in the matched cohort (7-day: 47.9% vs 39.6%, P = 0.35; 28-day: 56.3% vs 58.3%, P = 0.84). Mortality rates were similar between epinephrine- and vasopressin-exposed patients in propensity score–matched regression models with and without adjustments at 7 (relative risk [RR] = 1.28, 95% CI = 0.92-1.79; RR = 1.21, 95% CI = 0.81-1.81) and 28 days (RR = 1.04, 95% CI = 0.81-1.34; RR = 0.96, 95% CI = 0.69-1.34). Conclusion and Relevance: Shock-free survival durations were similar in matched epinephrine- and vasopressin-exposed groups. Adjuvant epinephrine or vasopressin alongside norepinephrine to raise MAP to target requires further investigation.