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Postmortem diagnosis of sudden death due to anaphylaxis can be very difficult due to the non-specific pathological findings in forensic practice. Postmortem serum tryptase has been used as an indicator of possible ante-mortem anaphylaxis. Though many previous studies have been conducted to explore the diagnostic significance of serum tryptase for lethal anaphylaxis, inconsistent results were documented. In this study, we made a retrospective study and presented a systematic review and meta-analysis that aims to summarize the diagnostic significance of postmortem serum tryptase in the deceased with and without anaphylactic shock and to calculate a cutoff value for future reference in the identification of deaths due to anaphylactic shock. A complete literature search in the PubMed, Cochrane Library, CNKI and Embase databases (published prior to March 1st, 2017) was performed. The quality of the eligible literature was evaluated according to the Newcastle-Ottawa Quality Assessment Scale (NOS), and the relevant data was extracted. The procedure of meta-analysis was performed by RevMan 5.3 software. Subgroup analysis was performed according to different causes of death. A total of nine studies with 296 patients were identified. The NOS of each included study was equal to 7. The results indicated that high concentrations of tryptase were significantly associated with anaphylactic shock when compared to the other causes of death. The weighted mean difference (WMD) was 29.53 (95% CI = 7.58-51.47, p = 0.008). Similar results were detected in the subgroup analysis when compared to deaths due to cardiovascular disease (CVD). However, no obvious elevation of tryptase in decedents with CVD compared to the other cause of death was observed (WMD = 4.42, 95% CI = -0.94-9.79). We concluded that high serum tryptase is a promising diagnostic biomarker for deaths due to anaphylactic shock, especially when it is higher than 30.4 μg/L.