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Aggressive approaches to acute diseases such as acute myocardial infarction, trauma, and stroke have improved outcomes. Early goal-directed therapy for severe sepsis and septic shock represents a similar approach. An analysis of the literature assessing external validity and generalizability of this intervention is lacking.Eleven peer-reviewed publications (1569 patients) and 28 abstracts (4429 patients) after the original early goal-directed therapy study were identified from academic, community and international settings. These publications total 5998 patients (3042 before and 2956 after early goal-directed therapy). The mean age, sex, APACHE II scores and mortality were similar across all studies. The mean relative and absolute risk reduction was 0.46 ± 26% and 20.3 ± 12.7%, respectively. These findings are superior to the original early goal-directed therapy trial which showed figures of 34% and 16%, respectively. A consistent and similar decrease in healthcare resource consumption was also found.Early goal-directed therapy modulates systemic inflammation and results in significant reductions in morbidity, mortality, and healthcare resource consumption. Early goal-directed therapy has been externally validated and is generalizable across multiple healthcare settings. Because of these robust findings, further emphasis should be placed on overcoming logistical, institutional, and professional barriers to implementation which can save the life of one of every six patients presenting with severe sepsis and septic shock.