Objective: To determine the effect of albumin administration on morbidity in acutely ill hospitalized patients. Data Source: Computer searches of MEDLINE, EMBASE, and the Cochrane Library; hand searches of journals and Index Medicus, inquiries with investigators and fluid product suppliers; and examination of reference lists. No language or time period restrictions were adopted. Study Selection: Randomized, controlled trials comparing the administration of albumin with that of crystalloid, no albumin, or lower-dose albumin. Data Extraction: Two investigators independently extracted data. The primary endpoint for the meta-analysis was morbidity, defined as the incidence of complications, including death. Trial quality was evaluated by blinding, allocation concealment, presence of morbidity as a study endpoint, and individual patient crossover. Data Synthesis: Seventy-one trials were included in the categories of surgery or trauma, burns, hypoalbuminemia, high-risk neonates, ascites, and other indications. The 3,782 randomized patients in the included trials experienced a total of 3,287 complications, including 515 deaths and 2,772 cardiovascular, gastrointestinal, hepatic, infectious, renal, respiratory, and other complications. Albumin significantly reduced overall morbidity, with a risk ratio of 0.92 (confidence interval [CI], 0.86-0.98). Control group albumin dose significantly affected the incidence of complications (p = .002). In 32 trials with no albumin administered to the control group, the risk ratio was 0.77 (CI, 0.67-0.88) compared with 0.89 (CI, 0.80-1.00) in 20 trials with control patients receiving low-dose albumin and 1.07 (CI, 0.96-1.20) in 19 trials with moderate-dose control group albumin. Conclusions., Albumin reduces morbidity in acutely ill hospitalized patients. Concomitant administration of albumin in the control group can obscure the effects of albumin on clinical outcome in randomized trials.