Central venous cannulation (CVC) is required for management of critically ill and hemodialysis patients which has different complications in conventional procedure. The aim of this study was to compare the outcomes and complication of central venous cannulation using both conventional and ultrasound guide. A randomized controlled trial study of 336 recently hospitalized hemodialysis patients was conducted (168 in intervention group and 168 in control group). CVC was done by an ultrasound machine in intervention group that the needle was inserted perpendicular to the skin under visualization on the US screen while CVC was performed by the conventional landmark approach in the other group. The time for insertion, attempts required, and complications were measured in both groups. Data were analyzed with ANOVA Repeated Measure. In intervention group 22 patients (13.09) required more than one attempt, while in the control group 75 patients (44.6) required more than one attempt. Statistically this difference was significant (P.V = 0.000). In the control group, arterial puncture was happened in 10 patients (5.9), and hematoma in 5 patient (2.9), while were 2 patients (1.1) and 1 patients (0.59) in the ultrasound group respectively (P.V = 0.04 and P.V = 0.05). The results of our study showed that USG approach took lesser time, required lesser attempts, and had lower incidence of complications for cannulation of the internal jugular vein.