Conducting health assessments and physical examinations are essential skills for independent practice. Exploring how to teach these skills effectively is essential. This study was designed to validate the effectiveness of a self-directed learning program in improving nursing student outcomes in terms of their learning health assessment and physical examination skills. A quasi-experimental design was used, and second-year nursing students enrolled in a health assessment and physical examination course at a university of science and technology in central Taiwan were recruited using purposive sampling. Both the control and experimental groups were taught using a traditional teaching method. The experimental group additionally participated in a self-directed learning program. Structured questionnaires, including the Chinese version of the Self-Directed Learning Readiness Scale, Scales of Motivation and Learning Strategies, Interpersonal Skills Assessment Tool, the Course Satisfaction Evaluation Scale, and the Perception of Health Assessment and Physical Examination Competence Scale, were used to collect data at three time points. After controlling for the effects of pretest scores, after the intervention, the experimental group achieved significantly higher scores than the control group for self-directed learning (creative learning and love of learning), learning motivation (goal orientation, work value, expected success, and test anxiety), and cognitive strategies (total score, elaboration strategy, recitation strategy, and monitoring strategy). In addition, the health assessment exercise improved interpersonal and communication skills, and learning satisfaction was significantly higher in the experimental group than the control group. A physical examination and health assessment course designed using the self-directed learning framework can effectively improve student competence in related skills to enhance their ability to assess patient health problems in clinical settings. This study presents an alternative approach to teaching health assessment and physical examination courses and validates the positive effect of this approach on student learning outcomes.