Background. Few studies have analyzed the negative outcomes of disruptive behaviors in the nurse-physician relationship in patient care and their impact on patient safety. These multicausal studies significantly relate to organizational, institutional, and professional attitudinal risk factors. Aim. Analyze healthcare professionals’ perceptions of disruptive behavior and factors associated with patient safety climate in the nurse-physician relationship at the hospital level. Methods. A multicenter cross-sectional study was conducted with a sample of 370 nurses and physicians assigned to different public hospitals in the Murcia/Spain region, applying the adapted and validated Spanish version of the Nurse-Physician Relationship Scale: Impact of Disruptive Behavior on Patient Care. The analysis used proportions or means (standard deviation (SD)), univariate and multivariate linear regression models, and the chi-square test. Results. Disruptive behavior was more prevalent in the ICU (81.6%) and the emergency department (67.8%). Professionals indicate that fear of reprisals is the main barrier to the reporting system. Likewise, stress and frustration are more associated with disruptive behavior and influence the safety climate. Conclusion. Professionals indicate that disruptive behaviors can have a negative impact on clinical outcomes. Age and type of service were identified as the most relevant socio-occupational factors. Stress, frustration, and communication problems are the factors that most influence the safety climate.