Patient safety becomes topmost priority-almost always comparable to the quality of healthcare in the facade of disturbing rates of hospital imprecisions and resultant deaths. Expansive clinical experience, exposure to evidencebased practices and active research engagement can potentially address these problematic consequences. This descriptive-correlational study identified the 304 registered nurses' professional core competencies from selected government and non-government hospitals in the Philippines and determined their impact on KPIs for patient safety outcomes. Most of the nurses' professional core competencies displayed very high grade (x=3.52, SD±0.090) specifically on safe nursing practice (x=3.88, SD±0.087, very high) followed by leadership and management (x=3.68, SD±0.086, very high) and research (x=3.01, SD±0.097, high). KPIs showed an overall mean score of 3.17 (SD±0.418, high) and among the five (5) indicators, blood management (x=3.45, SD±0.0611, very high) and medication safety (x=3.55, SD±0.493, very high) obtained the highest scores. Finally, a significant relationship exists between the nurses' professional core competencies and KPIs for patient safety outcomes and further disclosed a highly positive correlation (r-0.950, p=0.000) that undoubtedly determined the impact of professional core competencies on KPIs. Ultimately, the results concluded the vital importance of safe nursing practice, research, leadership, and management, as professional core competencies in ensuring patient safety in hospitals.