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Eligible studies were hERG assays reporting half\u2010minimal inhibitory concentrations (IC50). A \u201chERG safety margin\u201d was calculated from the IC50 divided by the peak human plasma concentration (free C<jats:sub>max<\/jats:sub>). A margin below 30 defined hERG liability. Each drug was assigned an \u201cuncertainty score\u201d based on volume, consistency, precision, and internal and external validity of evidence. The hERG liability was compared to existing knowledge on TdP risk (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.credibledrugs.org\">www.credibledrugs.org<\/jats:ext-link>). Of 1828 studies, 82 were eligible, allowing calculation of safety margins for 61 drugs. Thirty\u2010one drugs (51%) had evidence of hERG liability including 6 with no previous mention of TdP risk (eg, desloratadine, lopinavir). Conversely, 16 drugs (26%) had no evidence of hERG liability including 6 with known, or at least conditional or possible, TdP risk (eg, chlorpromazine, sulpiride). The main sources of uncertainty were the validity of the experimental conditions used (antihistamines and antipsychotics) and nonuse of reference compounds (anti\u2010infectives). In summary, hERG liability was categorized for 3 widely used drug classes, incorporating a qualitative assessment of the strength of available evidence. Some concordance with TdP risk was observed, although several drugs had hERG liability without evidence of clinical risk and vice versa. 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