Medical device-related pressure injuries (MDRPIs) are a patient safety concern in acute and critical care settings. Registered nurses must implement preventive strategies, yet gaps remain in their knowledge, attitudes, and clinical practices related to MDRPI prevention. This study aimed to evaluate the effectiveness of a structured educational intervention in improving registered nurses' knowledge, attitudes, and practices related to MDRPI prevention. A quasi-experimental pre–post intervention study was conducted in a tertiary care hospital in Saudi Arabia, with 311 registered nurses participating. Data were collected using a questionnaire assessing knowledge, attitudes, and practices related to MDRPI prevention. Participants received a one-day structured educational program based on the knowledge, attitude, practice (KAP) framework and the evidence-based SKINCARE bundle. The educational intervention resulted in significant improvements. Mean scores increased from 14.17 (SD = 2.38) pre-intervention to 16.25 (SD = 1.97) post-intervention (t = −11.81, p < 0.001). The intervention demonstrated a moderate-to-large effect size (Cohen's d = 0.67), indicating meaningful improvement in nurses' preventive competencies. Structured educational programs can enhance registered nurses' knowledge and practices in MDRPI prevention. Integrating evidence-based training programs into routine hospital education may strengthen pressure injury prevention guidelines and improve patient safety outcomes.