Acoustic cardiography can provide simultaneous electrocardiography and acoustic cardiac data to assess the electronic and mechanical heart functions. The aim of this study was to assess whether changes in acoustic cardiographic parameters (ACPs) before and after hemodialysis (HD) are associated with overall and cardiovascular (CV) mortality in HD patients. A total of 162 HD patients was enrolled and ACPs were measured before and after HD, including left ventricular systolic time (LVST), systolic dysfunction index (SDI), third (S3) and fourth (S4) heart sounds, and electromechanical activation time (EMAT). During a follow-up of 2.9 years, 25 deaths occurred with 16 from CV causes. Multivariate analysis showed that high △SDI (per 1; hazard ratio [HR], 2.178; 95% confidence interval [CI], 1.189-3.990), high △EMAT (per 1%; HR, 2.218; 95% CI 1.382-3.559), and low △LVST (per 1 ms; HR, 0.947; 95% CI 0.912-0.984) were independently associated with increased overall mortality. In addition, high △EMAT (per 1%; HR, 2.141; 95% CI 1.117-4.102), and low △LVST (per 1 ms; HR, 0.777; 95% CI 0.637-0.949) were associated with increased CV mortality. In conclusion, the changes in ACPs before and after HD may be a useful clinical marker and stronger prognostic marker of overall and CV mortality than ACPs before HD.