Background: The conventional written tests and professional assessment have limitation in fair judgement of clinical competence. Because the examiners may not have total objectivity and may lack standardization throughout the assessment process. We sought to design a valid method of competence assessment in medical and nursing specialties. This work was aimed to develop an Objective Structured Clinical Exam (OSCE) to evaluate novice nursing practitioners’ (NNPs’) clinical competency, work stress, professional confidence, and career satisfaction. Methods: A Quasi-experimental study (pre-post). Fifty-five NNPs received the OSCE three-months following their graduation, which consisted of four stations: history taking, physical examination, problem-directed management, interpersonal communication, and the required techniques of related procedures. The examiners had to complete an assessment checklist, and the participants had to complete a pre-post questionnaire (modified from a Nursing Competency Questionnaire, a Stress scale, and Satisfaction with Learning scale). Results: Among the NNPs, 41 of them (74.5%) passed the exam with a mean score of 61.38 ± 8.34. There was a significantly higher passing rate among nurses who were working in medical-surgical wards (85.7%) and the intensive care unit-emergency department (77.8%) compared to NNPs working in other units. All the NNPs at Station A had poor performance in assessing patients with a fever. OSCE performance was more associated with educational attainment and work unit, rather than the gender. Finally, the participants showed statistically significant increases in their clinical competency, confidence in their professional competence, satisfaction with the clinical practice, and decreased work stress after the OSCE. Conclusions: We found that the OSCE process had a positive educational effect, in providing a meaningful and accurate assessment of the competence of NNPs. Although the implementation of an OSCE remains costly, the consequent benefits for NNPs, educators, and administrators can outweigh its costs, demonstrated by the increased competence and workforce stability following OSCE training.