OBJECTIVE: The aim of this study was to investigate the left-ventricular (LV) mass-adjusted association between low heart rate variability (HRV) and atherosclerotic cardiovascular disease (ASCVD) among hemodialysis patients in Kuwait. SUBJECTS AND METHODS: One hundred and eight patients were enrolled in the study. HRV time domain measures were obtained by 48-hour Holter monitoring, including the standard deviation of all R-wave-to-R-wave (RR) intervals (SDNN), standard deviation of all 5-min averaged intervals (SDANN), HRV triangular index (HRV-TI), percent of adjacent RR intervals differing by >50 ms (pNN50), and root mean square of sums of squares of all differences (rMSSD). Left ventricular ejection fraction (LVEF) and LV mass index (LVMI) were measured by M-mode echocardiography. Comorbidity was assessed using medical record review. Prevalent ASCVD was defined as coronary artery, cerebrovascular, or peripheral vascular disease. RESULTS: Prevalence of ASCVD, LV hypertrophy, and LVEF <40% were 56, 59, and 10%, respectively. The SDANN was negatively associated with ASCVD (-20 ms; p = 0.003), LV systolic dysfunction (-20 ms; p = 0.001), elevated LVMI (-20 ms; p = 0.002), hypertension (-34 ms; p = 0.01), and diabetes (-20 ms; p = 0.001). After adjustment for hypertension and LVMI using logistic regression, ASCVD was associated with the lowest quartile of SDANN (OR = 4.3, p = 0.009), HRV-TI (OR = 3.3, p = 0.03), and SDNN (OR = 2.3, p = 0.10). These associations persisted after adjusting for LVEF. CONCLUSION: In dialysis patients, low HRV indices were strongly associated with prevalent ASCVD, independent of LVMI and LVEF. The interrelationships among HRV, diabetes, hypertension, and LVMI should be addressed in studies of HRV and ASCVD.