Background:This meta-analysis was to determine the association of the cumulative dose of 130/0.4 or 0.42 (hydroxyethyl starch [HES] 130/0.4*) or delta daily fluid balance (i.e.,daily fluid balance in HES group over or below control group) with the heterogeneity of risk ratio (RR) for mortality in randomized control trials (RCTs).Methods:Three databases (PubMed,EMBASE,Cochrane) were searched to identify prospective RCTs reporting mortality in adult patients with sepsis to compare HES 130/0.4* with crystalloids or albumin.Meta-analysis was performed using random effects.Sensitivity and meta-regression analyses were used to examine the heterogeneity sources of RR for mortality.Results:A total number of 4408 patients from 11 RCTs were included.The pooled RR showed no significant difference for overall mortality in patients with administration of HES130/0.4* compared with treatment of control fluids (RR:1.02,95％ confidence interval:0.90-1.17;P =0.73).Heterogeneity was moderate across recruited trials (I2 =34％,P =0.13).But,a significant variation was demonstrated in subgroup with crystalloids as control fluids (I2 =42％,P ＜ 0.l).Sensitivity analysis revealed that trials with high risk of bias did not significantly impact the pooled estimates for mortality.Meta-regression analysis also did not determine a dose-effect relationship of H ES130/0.4* with mortality (P =0.298),but suggested daily delta fluid balance being likely associated with mortality in septic patients receiving HES 130/130/0.4* (P =0.079).Conclusions:Inappropriate daily positive fluid balance was likely an important source of heterogeneity in these trials reporting HES 130/0.4* associated with excess mortality in septic patients.