Communication is the basis of nursing care and can have a significant effect on patient and community health. This study aimed to optimize the professional and interprofessional relationships of nurses. This participatory action research was conducted with 288 patients and 23 staff of one of the Reference Hospitals in Tehran, Iran, from 2019 to 2020. Interviews were simultaneously analyzed using the conventional content analysis method, and in the quantitative section, the communication skills checklist and a researcher-made questionnaire were used. Participants gave oral and written consent, and their confidentiality and anonymity were respected. Participants’ experiences showed that the implemented programs changed the work environment. The acquired basic concepts were improving the nurse’s responsibility and accountability, improving the quality of care and respecting the patient and the family. Quantitative data obtained before and after the implementation of change programs showed that patient satisfaction increased from 41.57±7.03 to 94.34±4.67 and patient and family training from 113.73±19.77 to 245.99±36.61. The length of hospital stay decreased from 5.52±2.47 to 3.57±2.35 days, nosocomial infections from 32.1±2.8 to 17.4±2.4 and readmission from 4.8±1.2 to 2.3±1.1. The results indicated that patients’ quality of care and safety was increased by optimizing the nurse’s professional and interprofessional relationship. Patients reported greater respect, and nurses had higher job satisfaction.