Central venous stenosis (CVS) is usually a late-diagnosed clinical entity that is common in hemodialysis patients. It causes various problems ranging from hemodialysis difficulty to loss of the arterio–venous (A–V) fistula. In the present study, we aimed to determine the effect of drug eluting balloon while excluding the influence of other variable factors by evaluating the same individuals with plain and paclitaxel-eluting balloons. This research was a prospective study of 18 symptomatic hemodialysis patients (age 50.9 ± 14.0 years, range 32–72 years; 11 male, 7 female) with CVS who underwent treatment by plain balloon angioplasty (PBA) and paclitaxel-eluting balloon angioplasty (PEBA) in our hospital from January 2016 to June 2017. First, third and sixth month central vein patency rates were compared. The median patency rates of central veins were 109.0 (range: 10–324) days after PBA and 238.5 (range: 157–501) days after PEBA (p < 0.001). There was no statistically significant difference between PBA and PEBA angioplasty in one-month patency (p ˃ 0.05). By contrast, a statistically significant difference was found between 3- and 6-month patency rates (p = 0.031 and p ˂ 0.001, respectively). Kaplan–Meier analysis revealed that the primary cumulative patency rate of PEBA was significantly longer than that of PBA (p ˂ 0.001). In this prospective study, PEBA patency is superior to PBA patency in the treatment of CVS in dialysis patients.