BACKGROUND: Prior studies have shown that women have worse 3-month survival after receiving a left ventricular assist device compared with men. Currently used prognostic scores, including the Heartmate II Risk Score, do not account for the increased residual risk in women. We used the IMACS (International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support) registry to create and validate a sex-specific risk score for early mortality in left ventricular assist device recipients. METHODS AND RESULTS: Adult patients with a continuous-flow LVAD from the IMACS registry were randomly divided into a derivation cohort (DC; n=9113; 21% female) and a validation cohort (VC; n=6074; 21% female). The IMACS Risk Score was developed in the DC to predict 3-month mortality, from preoperative candidate predictors selected using the Akaike information criterion, or significant sex × variable interaction. In the DC, age, cardiogenic shock at implantation, body mass index, blood urea nitrogen, bilirubin, hemoglobin, albumin, platelet count, left ventricular end-diastolic diameter, tricuspid regurgita-tion, dialysis, and major infection before implantation were retained as significant predictors of 3-month mortality. There was significant ischemic heart failure × sex and platelet count × sex interaction. For each quartile increase in IMACS risk score, men (odds ratio [OR], 1.86; 95% CI, 1.74– 2.00; P<0.0001), and women (OR, 1.93; 95% CI, 1.47– 2.59; P<0.0001) had higher odds of 3-month mortality. The IMACS risk score represented a significant improvement over Heartmate II Risk Score (IMACS risk score area under the receiver operating characteristic curve: men: DC, 0.71; 95% CI, 0.69– 0.73; VC, 0.69; 95% CI, 0.66– 0.72; women: DC, 0.73; 95% CI, 0.70– 0.77; VC, 0.71 [95% CI, 0.66– 0.76; P<0.01 for improvement in receiver operating char-acteristic) and provided excellent risk calibration in both sexes. Removal of sex-specific interaction terms resulted in significant loss of model fit. CONCLUSIONS: A sex-specific risk score provides excellent risk prediction in LVAD recipients.