Background Patients with cirrhosis have immune dysfunction, altered inflammatory response, and hemodynamic changes which increase risk of septic shock and potentially prolong management with fluids, vasopressors, and other therapies. Due to limited available guidance, this study aimed to characterize vasopressor use in patients with cirrhosis in relation to patients without cirrhosis in septic shock. Methods This was a retrospective matched cohort analysis of 122 patients admitted to the intensive care unit (ICU) at an academic medical center from January 2015 to November 2017. Patients were grouped based on the presence or absence of cirrhosis and matched based on severity of illness scoring. The primary outcome was vasopressor duration. Secondary comparisons included total vasopressor requirement, length of hospital and ICU stay, in-hospital mortality, change in organ function, and discharge disposition. Results The group with cirrhosis had significantly longer median (interquartile range [IQR]) durations of vasopressor therapy compared with the group without cirrhosis (86.0 [42.0-164.5] vs 39.0 [14.5-82.0] hours; P = 0.003) leading to increased median (IQR) vasopressor exposure (71.7 [15.5-239.5] vs 24.7 [5.3-77.9] mg norepinephrine [NE] equivalents; P = 0.003). No difference was found in in-hospital mortality between groups. However, regression analysis showed vasopressor exposure was associated with in-hospital mortality. Conclusion and Relevance Patients with cirrhosis in septic shock have increased vasopressor durations and overall requirements compared with patients without cirrhosis. Increased durations and requirements is associated with poorer outcomes independent of presence of cirrhosis. Future studies are needed to improve vasopressor treatment strategies and end points utilized in cirrhosis.