Few studies were performed to investigate the association between tissue Doppler imaging parameters about left ventricular (LV) systolic function and LV systolic asynchrony and prognosis in patients with septic shock and normal LV ejection fraction (LVEF). This prospective study was performed from January 2010 to April 2012 in a medical intensive care unit. Fifty-one patients with septic shock and LVEF greater than or equal to 50% were analyzed. The clinical variables and transthoracic echocardiography data were obtained on admission. The mean value of the peak myocardial systolic velocity (Sm-mean) was measured in the four LV basal segments. Tissue Doppler imaging-based parameter (Ts-SD) was used to evaluate LV intraventricular asynchrony. The 28-day all-cause mortality was 43.1%. The nonsurvivors exhibited higher baseline heart rate and Sm-mean and lower mean arterial blood pressure and Ts-SD. A cutoff value of Sm-mean greater than or equal to 6.2 cm/s in identifying 28-day mortality was determined by the receiver operating characteristic curve analysis. The patients with Sm-mean greater than or equal to 6.2 cm/s or Ts-SD less than 33 ms had higher 28-day mortality. In the Cox multivariate analysis, Sm-mean, Ts-SD, and mean arterial blood pressure emerged as independent predictors for 28-day mortality. We concluded that LV systolic dysfunction and systolic asynchrony assessed by tissue Doppler imaging were associated with improved 28-day all-cause mortality in patients with septic shock and normal LVEF.