Objectives: Successful placement of a peripheral intravenous catheter (PIVC) on the first attempt is an important outcome for difficult vascular access (DVA) patients. This study compared standard technique, ultrasonography (USG), and near-infrared light (NIR) in terms of success in the first attempt in patients with DVA. Methods: This was a prospective, randomized controlled study. The study was conducted in a tertiary care hospital. Emergency department patients who describe DVA history, have no visible or palpable veins, and were assessed by the nurse to have a difficult PIVC were included to study. The PIVC procedure was performed on patients by standard, USG, or NIR device techniques. For all approaches, the success of the first attempt was the primary aim. Total procedure time, the total number of attempts, and the need for rescue intervention were secondary aims. Results: This study evaluated 270 patients. The first attempt success rates for USG, standard, and NIR methods were 78.9%, 62.2%, and 58.9%, respectively. The rate of first attempt success was higher in patients who underwent USG (USG versus standard, P = .014; USG versus NIR, P = .004; standard versus NIR, P = .648). The total median (IQR) procedure time for USG, standard, and NIR methods was 107 (69-228), 72 (47-134), and 82 (61-163) seconds, respectively. The total procedure time was longer in patients undergoing USG (standard versus USG, P <.001; NIR versus USG, P = .035; standard versus NIR, P = .055). The total median (IQR) number of attempts of USG, standard, and NIR methods were 1 (1-1), 1 (1-2), and 1 (1-2), respectively. A difference was found among the groups regarding the total number of attempts (USG versus NIR, P = .015; USG versus standard P = .108; standard versus NIR, P = .307). No difference was found among groups in terms of the need for rescue methods. Conclusion: It was found that USG increases the success of the first attempt compared with the standard method and NIR in patients with DVA.