Background/Objectives: High turnover and staff shortages in nursing pose challenges to professional integration and compromised patient safety. Structured onboarding programs are considered key strategies to enhance adaptation, reduce clinical errors, and promote retention. This study aimed to evaluate the impact of a structured onboarding program compared with the standard routine on early professional adaptation, safety culture, and satisfaction among newly hired nurses and nursing assistants. Methods: A prospective quasi-experimental study was conducted between 2022 and 2024 in three private hospitals in Madrid. A total of 200 newly hired health professionals (128 nurses and 72 assistants) were assigned alternately to either the intervention group (structured onboarding program) or the control group (usual routine). The intervention comprised three consecutive days of guided training with mentorship, simulation-based learning, and digital tool instruction. Adaptation was assessed with the validated GAML scale, and satisfaction was measured through a Likert survey one month later. Statistical analyses included Mann–Whitney U, Chi-squared tests, and linear regression. Results: The intervention group achieved significantly higher scores across all competency domains for both nurses and nursing assistants, with overall medians of 25 [22–27] and 22 [20–23.25], respectively, compared with notably lower values in the control groups (p < 0.001). The greatest improvements were observed in digital tool management, clinical protocol knowledge, problem-solving and decision-making, and patient safety practices, demonstrating the strong impact of the structured onboarding program. In terms of satisfaction, participants in the intervention group also reported higher ratings for the clarity and completeness of information, particularly regarding hospital structure, service-specific orientation, and occupational risk prevention. However, global satisfaction differences were more pronounced among nurses than nursing assistants. Conclusions: The structured onboarding program demonstrated substantial benefits in professional adaptation, safety culture, and perceived preparedness of newly hired staff. These findings support integrating standardized onboarding plans as part of hospital quality and safety strategies, requiring sustained leadership and resource investment for long-term success.
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