BACKGROUND: The overall clinical decision limits of high-sensitivity cardiac troponin I (hs-cTnI; 26 ng/L) and T (hs-cTnT; 14 ng/L) may contribute to underdiagnosis of acute myocardial infarction in women. We performed a systematic review to investigate sex-specific and overall 99th percentiles of hs-cTnI and hs-cTnT derived from healthy reference populations. CONTENT: We searched in PubMed and EMBASE for original studies, and by screening reference lists. Reference populations designed to establish 99th percentiles of hs-cTnI (Abbott) and/or hs-cTnT (Roche), published between January 2009 and October 2017, were included. Sex-specific and overall 99th percentile values of hs-cTnI and hs-cTnT were compared with overall clinical decision ranges (hs-cTnI, 23-30 ng/L; hs-cTnT, 13-25 ng/L). Twenty-eight studies were included in the systematic review. Of 16 hs-cTnI and 18 hs-cTnT studies, 14 (87.5%) and 11 (61.1%) studies reported lower femalespecific hs-cTn cutoffs than overall clinical decision ranges, respectively. Conversely, male-specific thresholds of both hs-cTnI and hs-cTnT were in line with currently used overall thresholds, particularly hs-cTnT (90% concordance). The variation of estimated overall 99th percentiles was much higher for hs-cTnI than hs-cTnT (29.4% vs 80.0% of hs-cTnI and hs-cTnT studies reported values within the current overall clinical decision range, respectively). SUMMARY: Our data show substantially lower femalespecific upper reference limits of hs-cTnI and hs-cTnT than overall clinical decision limits of 26 ng/L and 14 ng/L, respectively. The statistical approach strongly affects the hs-cTnI threshold. Downward adjustment of hs-cTn thresholds in women may be warranted to reduce underdiagnosis of acute myocardial infarction in women.