OBJECTIVES: To determine whether the early use of albumin after cardiac surgery in the first 24 hours in the intensive care unit (ICU) is associated with reduced mortality. DESIGN: A single-center nonrandomized retrospective cohort study using the Medical Information Mart in Intensive Care IV database. SETTING: A single cardiothoracic ICU in the United States during a period between 2008 to 2019. PARTICIPANTS: Patients undergoing valvular and/or cardiac bypass graft surgeries. INTERVENTIONS: Albumin administered during the first 24 hours of the ICU admission. MEASUREMENTS AND MAIN RESULTS: A total of 8,136 patients were included in this study, of whom 4,444 (54.6%) received albumin at any stage during the first 24 hours of ICU admission, and 69 (1.6%) of those patients died. The patient population exposed to albumin had higher comorbidities and illness severity compared to the no-albumin group. Patients exposed to albumin during the first 24 hours of ICU admission had a statistically significant reduction in mortality (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.48-0.97, p < 0.05) after adjustment for age, the Oxford Acute Severity of Illness Score, and the Charlson comorbidity index. A sensitivity analysis of patients who received albumin at any stage during ICU admission showed increased mortality (OR, 1.93; 95% CI, 1.26-3.07, p < 0.01). Patients exposed to albumin had a significant increase in adjusted ICU length of stay (LOS) (geometric mean ratio 1.09; 95% CI, 1.05-1.10, p = < 0.001) and hospital LOS (geometric mean ratio 1.08; 95% CI, 1.05-1.10, p < 0.001). CONCLUSIONS: Exposure to albumin in the first 24 hours after cardiac surgery is associated with a reduction in adjusted hospital mortality and an increase in both hospital and ICU lengths of stay.