This study aimed to evaluate the efficacy and safety of ultrasound-guided out-of-plane internal jugular vein (OOP-IJV) versus in-plane supraclavicular subclavian vein (IP-SSCV) catheterization in adult intensive care units. Using a random number generator, 250 consecutive patients in need of a central venous catheter were split evenly between 2 groups: those who had ultrasound-guided OOP-IJV cannulation and those who had IP-SSCV cannulation. There were 3 doctors involved in all of the catheterizations. The rate of success on the first try was the most important metric. Time spent on ultrasound scans, time spent on the venous puncture, time spent inserting the catheter, total time spent gaining access, number of puncture tries, number of needle re-directions, success rate, guidewire progressing issues, venous collapse, and adverse events were all recorded. The first attempt success rate was significantly higher in the IP-SSCV group (83.2%) compared to the OOP-IJV group (63.2%) (P = 0.001). Ultrasound scanning took longer in the IP-SSCV group (16.54 ±13.51  vs. 5.26±  4.05 s; P<0.001), but less time was spent inserting the catheter (43.98± 26.77 vs. 53.12   40.21 s; P = 0.038). Fewer puncture attempts were made in the IP-SCCV group (1.16 ± 0.39 vs. 1.47 ±0.71 ; P<0.001), and fewer needle redirections were made (0.69 ±0.58 vs. 1.17 ±0.95; P <0.001), and fewer issues were encountered with guidewire advancement (2.4% vs. 27.4%; P <0.001), venous collapse (2.4%, vs. 18.4; P<0.001 and adverse events (8.8% vs. 13.6%; P = 0.22). When applied to critically ill adults, the IP-SSCV technique offers a reliable and secure alternative to traditional OOP-IJV catheterization.