Several studies indicate that norepinephrine (NE) may be more effective than dopamine for the treatment of septic shock. Nonetheless, many consider dopamine to be the pressor of choice for shock refractory to volume resuscitation. Owing to fear of excessive vasoconstriction, accentuated end-organ hypoperfusion, and the development of multiple organ dysfunction syndrome (MODS), it is contended that NE may be deleterious. We analyzed the duration of NE use and the variables that predict mortality in a consecutive cohort of 406 surgical intensive care unit patients treated with NE for shock. Study parameters included age, acute physiology and chronic health evaluation (APACHE) II and APACHE III scores, hospital (HLOS) and intensive care unit (ULOS) length of stay, maximal and daily multiple organ dysfunction (MOD) scores, MOD score minus cardiovascular points (MOD-CV), duration of NE infusion, and survival. The duration of NE infusion was stratified into six subsets (1, 2, 3–5, 6–10,11–20, and ≥21 days). An age- and APACHE II and III score-matched cohort of 195 patients, in whom NE was not utilized, was identified retrospectively for comparison. The prevalence of NE use was 10.9%. NE patients developed MODS to a greater degree (11.7 ± .3 vs. 5.9 ± .4 points, p < .0001). NE patients had a greater degree (p < .0001) of noncardiovascular MOD as well. When stratified by survival, a greater degree of MOD occurred in both nonsurvivors and survivors of NE (both, p < .0001) compared with comparably ill patients without pressor-dependent shock. MOD scores, ULOS, and HLOS increased progressively with prolonged NE therapy (all, p < .0005), whereas mortality increased significantly only when the duration of NE infusion exceeded 10 days (p = .05). By multivariate analysis of variance (ANOVA), MOD score (p < .0001), and APACHE III (p < .01) predicted mortality, but notably the duration of NE therapy failed to attain predictive value (p = .3192). Only the MOD score was predictive of HLOS (p = .0001) and ULOS (p = .003). Daily MOD scores revealed that nonsurvivors of NE therapy were admitted to the intensive care unit with a greater degree of baseline organ dysfunction than NE survivors (7.5 ± .4 vs. 5.1 ± .2 for survivors, p < .0001). In addition, whereas survivors showed significant improvement by Day 5 (p < .01), MOD amongst nonsurvivors remained unchanged (p = .993). Although critically ill surgical patients requiring NE support have significantly greater degrees of organ dysfunction than patients not requiring pressors, much of the organ dysfunction is present on admission. The data contradict the notion that NE facilitates the development of MODS.