Objective To determine the influence of continuous mild sedation versus usual sedation on the sedative effect and inflammatory factor level in ICU patients with multiple trauma.Methods In this prospective, randomized double-blind investigation, 58 multiple trauma patients hospitalized from October 2013 to April 2015 were randomized into continuous mild sedation group (continuous group, n =30) and conventional sedation group (conventional group, n =28) using the sealed envelopes.Between-group differences were made on the duration of mechanical ventilation, length of stay in the ICU, ratio of inception of continuous renal replacement therapy (CRRT), tracheotomy rate, accidental extubation rate, sepsis rate, multiple organ failure (MOF) rate and mortality.Serum inflammatory factor levels of the patients were recorded.Results There were 3 deaths (10％) in continuous group versus 4 deaths (14％) in conventional group (P ＞ 0.05).Patients in continuous group showed significantly less time spent on mechanical ventilation [(4.8 ±2.7) vs.(8.9 ±3.1)d] and in the ICU [(10.7 ± 5.4) vs.(16.9 ± 7.3) d] compared with conventional group (P ＜ 0.01).Between-group differences were insignificant regarding the ratio of CRRT inception, tracheotomy rate, accidental extubation rate, sepsis rate and MOF rate (P ＞ 0.05).Serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, Creactive protein (CRP) were lower in continuous group than those in conventional group at 24 h, 48 h and 72 h post-ICU, but significant differences were only observed at 48 h (P ＜ 0.05).At these time periods, serum IL-10 levels in continuous group were significantly higher than those in conventional group (P ＜0.05).In receiver operative characteristic curve (ROC) analysis, the area under the curve for IL-6, IL-10, TNF-α and CRP in continuous group was 0.726, 0.608, 0.729 and 0.757 respectively at 48 h post-ICU, indicating a predictive value of these markers for sepsis.Conclusion Continuous mild sedation results in shortened length of stay in the ICU and decreased inflammatory response in the treatment of patients with multiple trauma.