Background: The cross-sectional area of the subclavian vein (csSCV) is a crucial factor in the successful catheterization of the subclavian vein. This randomized controlled study investigated the effects of the csSCV on landmark-based subclavian vein catheterization. Methods: This study was performed using a two-stage protocol. During stage I, the csSCV was measured in 17 patients placed in the supine, 20°ipsilateral tilt, and 20°contralateral tilt positions in a random order. During stage II, landmark-based subclavian vein catheterization was randomly performed in patients placed in either the supine (group S, n = 107) or the ipsilateral tilt (group I, n = 109) position. The primary outcome measure was the csSCV in stage I and the primary venipuncture success rate in stage II. Secondary outcome measures were the time to successful venipuncture, the total catheterization time, the first-pass success rate, and the incidence of mechanical complications during catheterization. Results: The csSCV was significantly larger in the ipsilateral tilt than in either the supine or contralateral tilt position (1.01 ± 0.35 vs. 0.84 ± 0.32 and 0.51 ± 0.26 cm 2 , P = .006 and < .001, respectively). The primary venipuncture success rate did not differ significantly between the group S and I (57.0 vs. 64.2%, P = .344). There were also no significant differences in the secondary outcome measures of the two groups. Conclusions: The csSCV was significantly larger in patients placed in the ipsilateral tilt than in the supine position, but the difference did not result in better clinical performance of landmark-based subclavian vein catheterization. Trial registration: NCT03296735 for stage I (ClinicalTrials.gov, September 28, 2017) and NCT03303274 for stage II (ClinicalTrials.gov, October 6, 2017).