Despite the implementation of safety-engineered devices (SEDs), needlestick injuries (NSIs) remain a leading cause of harm to healthcare personnel. This study analyzes the usability and safety of intravenous catheters (n = 17) with safety mechanisms. The analysis is based on a comparative usability test with healthcare workers (n = 44) and an expert evaluation with nine experts. Each product was tested by ten participants performing nine tasks in a usability laboratory. Two observers assessed effectiveness by measuring success rate (SR) and task completion time. Participants provided user satisfaction ratings by rating standardized post-task (SEQ) and post-test questionnaires. The usability of the SEDs varies significantly in terms of satisfaction. We discovered that passively activated SEDs have higher success rates than actively activated. In addition, the experts identified safety issues in 10 of the 17 products. Other usability problems occur during unpacking, venipuncture, and catheter fixation. By comparing 17 products, we present data that highlights the importance of choosing the right products to create safer workplaces. These findings are essential for both the development and selection of safer products in healthcare facilities’ procurement processes to reduce NSIs.