['Little is known about the factors associated with in-hospital mortality following total anterior circulation stroke (TACS). We examined the characteristics and comorbidity data for TACS patients in relation to in-hospital mortality with the aim of developing a simple clinical rule for predicting the acute mortality outcome in TACS.', 'A routine data registry of one regional hospital in the UK was analyzed. The subjects were 2,971 stroke patients with TACS (82% ischemic; median age=81 years, interquartile age range=74-86 years) admitted between 1996 and 2012. Uni- and multivariate regression models were used to estimate in-hospital mortality odds ratios for the study covariates. A 6-point TACS scoring system was developed from regression analyses to predict in-hospital mortality as the outcome.', 'Factors associated with in-hospital mortality of TACS were male sex [adjusted odds ratio (AOR)=1.19], age (AOR=4.96 for ≥85 years vs. <65 years), hemorrhagic subtype (AOR=1.70), nonlateralization (AOR=1.75), prestroke disability (AOR=1.73 for moderate disability vs. no symptoms), and congestive heart failure (CHF) (AOR=1.61). Risk stratification using the 6-point TACS Score [T=type (hemorrhage=1 point) and territory (nonlateralization=1 point), A=age (65-84 years=1 point, ≥85 years=2 points), C=CHF (if present=1 point), S=status before stroke (prestroke modified Rankin Scale score of 4 or 5=1 point)] reliably predicted a mortality outcome: score=0, 29.4% mortality; score=1, 46.2% mortality [negative predictive value (NPV)=70.6%, positive predictive value (PPV)=46.2%]; score=2, 64.1% mortality (NPV=70.6, PPV=64.1%); score=3, 73.7% mortality (NPV=70.6%, PPV=73.7%); and score=4 or 5, 81.2% mortality (NPV=70.6%, PPV=81.2%).'] Does a 6-Point TACS Score predict In-Hospital Mortality Following Total Anterior Circulation Stroke?