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There is debate as to the vasopressor agent of choice in patients with septic shock. According to current guidelines either dopamine or norepinephrine may be considered as the first-line agent for the management of refractory hypotension of septic shock.The aim of this systematic review was to evaluate randomized clinical trials which compared norepinephrine versus dopamine in critically ill patients with septic shock or in a population of critically ill patients with shock predominantly secondary to sepsis.MEDLINE, Embase, Scopus, Cochrane Register of Controlled Trials and citation review of relevant primary and review articles. Study Selection: Randomized clinical trials that compared norepinephrine with dopamine in critically ill adults with sepsis and reported the 28-day or in-hospital mortality.We abstracted data on study design, study setting, patient population, 28-day mortality or in-hospital mortality, rate of arrhythmias, hospital length of stay, and ICU length of stay.Six studies met our inclusion criteria. These studies included a total of 2043 participants, with 995 in the norepinephrine and 1048 in the dopamine groups. There were 479 (48%) deaths in the norepinephrine group and 555 (53%) deaths in the dopamine group. There was statistically significant superiority of norepinephrine over dopamine for the outcome of in-hospital or 28-day mortality: pooled RR: 0.91 (95% CI 0.83 to 0.99; P = .028). We also found a statistically significant decrease in the rate of cardiac arrhythmias in the norepinephine group as compared to the dopamine group: pooled RR: 0.43 (95% CI 0.26 to 0.69; P ≤ .001). A subgroup analysis that pooled studies in which all the randomized patients had septic shock demonstrated that norepinephrine improved in-hospital or 28-day mortality; however, the results were no longer statistically significant.The analysis of the pooled studies that included a critically ill population with shock predominantly secondary to sepsis showed superiority of norepinephrine over dopamine for in-hospital or 28-day mortality.