Indwelling venous catheters are invaluable for long-term chemotherapy, antibiotics, and hyperalimentation. However, their placement and chronic use can cause serious complications. This study was done to develop guidelines for minimizing complications of long-term vascular access. Complications associated with 355 lines placed in 297 patients were recorded prospectively at the George Washington University Hospital. Single or double lumen catheters were placed via the infraclavicular subclavian approach (126), external jugular cutdown (133), internal jugular cutdown (22), and cephalic vein cutdown (42). While catheters were malpositioned in 15 cases (5.2%), route of placement did not influence this adverse outcome. Pneumothorax occurred only in the subclavian approach (5.6%). Axillary vein thrombosis was significantly more prevalent in catheters placed via the subclavian vein (10.3%) compared with the external jugular (2.3%) P < 0.05 or cephalic (2.3%) vein. Line sepsis occurred in 28 instances; this was statistically associated with an abnormal white blood count and with the use of double-lumen catheters (double-lumen catheter sepsis = 18.4%, single lumen = 4.4%, P < 0.01). The morbidity of long-term venous catheters is affected significantly by the route of placement, the number of catheter lumens, and the pre-placement white blood count. As a result of our analysis, we recommend single-lumen catheter placement using the external jugular cutdown route whenever possible.