Background: Central venous access systems are frequently used for delivery of medications; however, few studies have compared surgical and postoperative complications of right versus left access via the subclavian vein (SCV). The aim of this study was to compare the surgical and postoperative complications associated with Port-A-Cath system insertion via the right and left SCV. Methods: The medical records of patients who received Port-A-Cath insertion via the SCV for parenteral chemotherapy between August 2004 and July 2008 were reviewed. The incidence of surgical and postoperative complications was compared between patients who received right- versus left-SCV Port-A-Cath insertion. Results: A total of 1,848 patients were included in the study. Right-SCV catheterization was attempted in 1,029 (55.7%) patients and was successful in 866 (84.2%). Left-SCV catheterization was attempted in 819 (44.3%) patients and was successful in 651 (79.5%). The mean length of postoperative follow-up was 417.3 ± 401.3 and 396.7 ± 379.9 days for the right- and left-SCV groups, respectively. The incidence of SCV puncture failure was significantly lower in the right-SCV group (12.3%) compared with the left-SCV group (16.8%, p = 0.006). The incidence of catheter knotting at the ipsilateral brachiocephalic vein was also significantly lower in the right-SCV group (0.0%) compared with the left-SCV group (0.5%, p = 0.038), as was the incidence of catheter occlusion (1.0% for right SCV vs. 3.5% for left SCV, p = 0.001). Conclusion: These findings suggest that the right-SCV approach is superior to the left-SCV approach for Port-A-Cath insertion.