The subclavian vein is frequently used to obtain central venous access. Several landmarks exist to determine the puncture site and angle, but they may require patient manipulation and anatomic measurements. We studied the feasibility of using the deltoid tuberosity, located on the lateral aspect of the clavicle, as an anatomic landmark. This would not necessitate these maneuvers and could therefore facilitate subclavian vein access. To systematically investigate this landmark, we conducted a study in four phases: 1) Two blindfolded examiners determined the distance between the tuberosity's medial border and the clavicle's lateral end in 100 dried clavicles and then 2) performed subclavian vein cannulation in 20 fresh human cadavers using the tuberosity and the suprasternal notch as landmarks. 3) Three-dimensional reconstructions of the subclavian artery and vein and surrounding structures were derived from computed tomography datasets of 10 patients. The length of the path of a virtual subclavian vein cannulation with the deltoid tuberosity landmark was measured bilaterally. 4) In a prospective, randomized trial, subclavian vein cannulation was performed in 60 patients with a standard approach or with the deltoid tuberosity as landmark. Interobserver difference between measurements in phase 1 was 3 +/- 1 mm (mean +/- sd); subclavian vein cannulation was achieved in 19 of 20 cases, whereas the subclavian artery was cannulated in one case (phase 2). In phase 3, there was no significant difference in skin-vein distance between the left (4.9 +/- 0.5 cm) and right (4.7 +/- 0.6 cm) sides. In phase 4, subclavian vein cannulation could be performed in all patients; moreover, subclavian vein cannulation was significantly (P < 0.01) faster in the deltoid tuberosity group versus the standard approach group (23 +/- 16 versus 34 +/- 14 s). We conclude that the clavicle's tuberosity may reflect an alternative anatomic landmark to simplify subclavian vein cannulation by minimizing patient manipulation and anatomic measurements.