Abstract—Echocardiographic left ventricular hypertrophy (Echo-LVH) and ST segment depression (STD) on the ECG have each been demonstrated to predict cardiovascular (CV) and all-cause (AC) mortality. However, the prognostic value of combining Echo-LVH and ECG-STD has not been examined. ECGs and echocardiograms were examined in 2193 American Indian participants in the second Strong Heart Study examination. STD was measured by computer and was considered abnormal if ≥50 &mgr;V. Echo-LVH was defined by indexed LV mass >116 g/m2in men and >104 g/m2in women. After a mean follow-up of 3.1±0.7 years, there were 57 CV and 169 AC deaths. In univariate Cox analyses, Echo-LVH (&khgr;2=54.2 and &khgr;2=68.5) and ECG-STD (&khgr;2=35.9 and &khgr;2=46.3, allP<0.001) predicted CV and AC mortality, respectively. The combination of Echo-LVH and ECG-STD improved risk stratification compared with either alone for both CV death (&khgr;2=74.4,P<0.001) and AC death (&khgr;2=102.0,P<0.001), with presence of both ECG-STD and Echo-LVH associated with the greatest risks. After adjustment for age, sex, and relevant risk factors, combined Echo-LVH and ECG-STD remained predictive of CV mortality (&khgr;2=19.7,P<0.001) and AC mortality (&khgr;2=24.9,P<0.001), with the presence of both Echo-LVH and ECG-STD associated with a 6.3-fold increased risk of CV death (95% CI: 2.8 to 14.2) and a 4.6-fold increased risk of AC mortality (95% CI: 2.5 to 8.5). ECG-STD and Echo-LVH additively increase the risk of both CV mortality and AC mortality. These findings support the value of combining Echo-LVH and ECG-STD to improve risk stratification. These findings require verification in other populations.