The outcome of allogeneic HSCT varies considerably by the disease and remission status at the time of transplantation. Any retrospective or prospective HSCT study that enrolls patients across disease types must account for this heterogeneity; yet, current methods are neither standardized nor validated. We conducted a retrospective study of 1539 patients who underwent transplantation at Dana-Farber Cancer Institute/Brigham and Women's Hospital from 2000 to 2009. Using multivariable models for overall survival, we created a disease risk index. This tool uses readily available information about disease and disease status to categorize patients into 4 risk groups with significantly different overall survival and progression-free survival on the basis of primarily differences in the relapse risk. This scheme applies regardless of conditioning intensity, is independent of comorbidity index, and was validated in an independent cohort of 672 patients from the Fred Hutchinson Cancer Research Center. This simple and validated scheme could be used to risk-stratify patients in both retrospective and prospective HSCT studies, to calibrate HSCT outcomes across studies and centers, and to promote the design of HSCT clinical trials that enroll patients across diseases and disease states, increasing our ability to study nondisease-specific outcomes in HSCT.