We sought to compare ultrasonography (US)-guided peripheral intravenous (PIV) access by regular technique using standard length catheters with a Seldinger technique using 16-cm central venous catheters in a randomized trial of adult patients with difficult intravenous (IV) access. Patients were randomized into two groups: (1) An US-guided IV access obtained through a regular technique or (2) An US-guided IV access obtained through a Seldinger technique. Outcomes measured were IV access success rates, number of attempts after enrollment, IV survival > 96 hours. As a secondary outcomes, we recorded IV complications rates and subject satisfaction. The two groups were matched in demographics, risk factors for difficult PIV access. No significant difference of clinical importance was found between the 2 groups in IV success rate or number of successful PIV catheter placement after one and two attempts. Median duration of access was 26 vs. 72 hours in regular technique group compared with Seldinger technique group, respectively. Forty one percent of IV catheters failed within 24 hours in regular technique group, most commonly due to infiltration with only 4.4 percent in Seldinger technique group. We observed low rate of immediate complications in both groups, however no infectious or thrombotic complication during the study period. Seldinger technique group had greater patient satisfaction compared with regular technique group. US-guided deep brachial or basilic vein cannulation with a 16-cm catheter offers a potentially safe and rapid alternative to central line placement in patients with difficult IV access.