Fall prevention represents a vital clinical indicator in healthcare settings and serves as a fundamental element of patient safety. This study aimed to evaluate nurses’ knowledge, attitude, and practices on fall prevention in caring for patients as well as explore the relationship between knowledge, attitude, and practices on fall prevention in patient care. This study was conducted on 312 nurses working in four selected level II government hospitals in Ho Chi Minh City from August to October 2024. The majority of nurses were female, with diplomas or BSNs, averaging 39.2 years old and 15.8 years of clinical experience. 77.9% attended a fall prevention training course. Most nurses showed moderate knowledge (66.7%) and practices (mean score of 3.26/5) regarding fall prevention, while their attitudes were generally positive (mean score of 3.92/5). Strong correlations were found between knowledge, attitude, and practices, as well as with prior training and education level (p < 0.001). Factors such as age, work experience, education, and training were predictive of fall prevention practices. Furthermore, attitude partially mediated the relationship between knowledge and practice. In summary, the study highlights the importance of fall prevention training, improving knowledge and attitudes, and considering factors like work experience and education in nursing practices. The mediating role of attitude suggests that fostering a positive attitude is key to better fall prevention practices, emphasizing the need for targeted educational programs that enhance both knowledge and attitudes to improve clinical outcomes.