Background— Timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients not on inotropes is unclear. Relevant prediction models exist (SHFM [Seattle Heart Failure Model] and HMRS [HeartMate II Risk Score]), but use in this group is not established. Methods and Results— ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) is a prospective, multicenter, nonrandomized study of 200 advanced heart failure patients not on inotropes who met indications for LVAD implantation, comparing the effectiveness of HeartMate II support versus optimal medical management. We compared SHFM-predicted versus observed survival (overall survival and LVAD-free survival) in the optimal medical management arm (n=103) and HMRS-predicted versus observed survival in all LVAD patients (n=111) using Cox modeling, receiver–operator characteristic (ROC) curves, and calibration plots. In the optimal medical management cohort, the SHFM was a significant predictor of survival (hazard ratio=2.98; P <0.001; ROC area under the curve=0.71; P <0.001) but not LVAD-free survival (hazard ratio=1.41; P =0.097; ROC area under the curve=0.56; P =0.314). SHFM showed adequate calibration for survival but overestimated LVAD-free survival. In the LVAD cohort, the HMRS had marginal discrimination at 3 (Cox P =0.23; ROC area under the curve=0.71; P =0.026) and 12 months (Cox P =0.036; ROC area under the curve=0.62; P =0.122), but calibration was poor, underestimating survival across time and risk subgroups. Conclusions— In non–inotrope-dependent advanced heart failure patients receiving optimal medical management, the SHFM was predictive of overall survival but underestimated the risk of clinical worsening and LVAD implantation. Among LVAD patients, the HMRS had marginal discrimination and underestimated survival post–LVAD implantation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01452802.