Myocardial and arterial load are time-varying phenomena. Despite their importance in myocardial function, the arterial properties that determine time-resolved myocardial wall stress are unknown. We aimed to assess arterial properties as determinants of time-resolved myocardial stress among 1214 men and women enrolled in the Asklepios Study. Time-resolved central pressure, flow, and left ventricular geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography, respectively, for computation of arterial load and ejection-phase time-varying myocardial wall stress. For any given end-diastolic left ventricular geometry and cardiac output, peak myocardial stress correlated directly with systemic vascular resistance (standardized β=1.12; P<0.0001) and aortic characteristic impedance (standardized β=0.17; P<0.0001). The ejection-phase stress-time integral correlated with systemic vascular resistance (standardized β=1.06; P<0.0001), lower total arterial compliance (standardized β=-0.13; P=0.0008), and earlier return of wave reflections (standardized β=-0.10; P<0.0001) but not with reflection magnitude, whereas end-systolic wall stress correlated with systemic vascular resistance (standardized β=1.06; P<0.0001) and reflection magnitude (standardized β=0.12; P<0.0001). After adjustment for age, all of the measured arterial properties, end-diastolic left ventricular geometry, and cardiac output, women demonstrated greater peak (534 versus 507 kdyne/cm(2); P<0.0001), end-systolic (335 versus 320 kdyne/cm(2); P<0.0001), and ejection-phase stress-time integral (157 versus 142 kdyne · s · cm(-2); P<0.0001). In conclusion, different arterial properties have selective effects on time-resolved ejection-phase myocardial wall stress, which are not apparent from single-time point measurements. Women demonstrate less efficient myocardial-arterial coupling, with higher wall stress development for any given left ventricular geometry, arterial properties, and flow output. These observations may relate to the differential susceptibility of women to heart failure.