In 2010, the FDA warned that tigecycline was associated with an increased risk of death. The risk factors of tigecycline-associated mortality are still controversial. The objective of this study was to obtain the clinical characteristics and to identify risk factors associated with mortality after tigecycline therapy. In an observational retrospective study, we compared the clinical characteristics of patients (non-survivor group) who died within 28 days after tigecycline therapy with those (survivor group) who survived within 28 days after tigecycline therapy. We used a logistic regression model to find risk factors of tigecycline associated mortality. 240 patients were included in the analysis, include 79 in the non-survivor group and161 in the survivor group. The proportion of the kidney failure events and change in creatinine value were greater in the non-survivor group after treated with tigecycline than in the survivor group (p < 0.001). In the multivariate analysis, age (p = 0.019), absolute value of the change of serum creatinine (?Cre) (p < 0.001), SCr (p = 0.038), APACHE II score (p = 0.031) were independently associated with mortality. An age of ? 79 years, ?Cre (?mol/L) ? 36, SCr ? 112 ?mol/L and APACHE II score ? 12.7 were selected as the cutoff points for predicting tigecycline associated mortality. The distribution of non-survivors at different ranges of creatinine change showed higher percentages of mortality with high ?Cre after tigecycline treatment. This study identifies the risk factors for tigecycline associated mortality, and draws attention to the fact that there is an increased mortality risk in patients treated with tigecycline.