Volume overload is thought to be the main cause of hypertension in dialysis patients. However, the effect of interdialytic weight gain (IDWG) in hemodialysis (HD) patients, which was considered as an increase in extracellular water (ECW), on blood pressure (BP) change, was controversial. Our aim was to examine the changes in hemodynamics and arterial stiffness during IDWG in HD patients and attempt to explore the possible mechanism of diverse BP change. Thirty prevalent patients on HD were enrolled. The height, weight, BP, blood chemistry, volume status assessed by bioelectrical impedance analysis, hemodynamic parameters obtained by echocardiography, and pulse wave velocity (PWV) were collected within 1 hour postdialysis and again just before the next dialysis session. Meanwhile, blood samples were drawn to analyze vasoactive hormones, including renin, angiotensin II, catecholamine, and endothelin. The patients' weights and ECWs during the next predialysis were significantly higher than those during the postdialysis. The BP showed no difference between postdialysis and the next predialysis. There was an obvious increase in cardiac output and decrease in total peripheral resistance as a whole during the next predialysis than that during postdialysis. When patients were divided into the BP increase group (BPI group, 13 patients) and BP decrease group (BPD group, 11 patients) according to the change in systolic BP higher than 10 mmHg, both groups displayed a significant increase in weight, ECW, cardiac output, and a decrease in total peripheral resistance. As compared with the BPI group, patients in the BPD group had significantly lower IDWG, shorter time on dialysis treatment, and higher residual renal function. A decrease in catecholamine and endothelin in the next predialysis was obvious in the BPD group. There was a significant decrease in PWV at the next predialysis in the BPD group while the PWV did not change significantly in the BPI group. Our results showed that the diverse BP change during IDWG was significantly affected by residual renal function, PWV, and vasoactive substances.