Background: Inter-professional collaboration ensures that healthcare teams play collaborative roles, share decisions, provide efficient care for patients, increase professional satisfaction, and reduce costs. Ineffective collaboration could result in costly medication errors and deaths associated with medical accidents. Objective: To assess inter-professional collaboration and associated factors among nurses and physicians working in comprehensive and teaching hospitals in the northwest Amhara region of Ethiopia in 2022. Method: This study used a mixed (institution-based cross-sectional and phenomenological qualitative) design. A structured self-administered nurse-physician collaborative scale questionnaire was used to collect quantitative data from 279 nurses and 87 physicians working in the Northwest Amhara region. A simple random sampling technique was used to select participants. The magnitude of association was measured using the odds ratio at a 95 % confidence interval and was statistically significant at a p-value less than 0.05 using multivariable logistic regression analysis. Qualitative data were collected from 9 key informants via interview guide and analyzed using ATLAS.ti version 7.0.7 software via narratives using the thematic analysis method. Result: According to the findings of the study, more than half of the respondents (56.6 %) had effective collaboration. Descriptive statistics like mean, frequency, and percentage were computed and displayed using text tables and graphs. In the final model of multivariable analysis, unsatisfactory organizational support, poor professional support, and poor interpersonal support were all independently associated with ineffective collaboration. The qualitative findings identified poor professional communication, lack of professionalism, and failure to adhere to professional duties as barriers to nurse-physician collaboration. Conclusion: in this study, nurse-physician collaboration was relatively effective. Potential predictors of decreased effective nurse-physician collaboration included an increase in dissatisfaction with organizational support, a decrease in professional support, and poor interpersonal support. This outcome emphasizes the importance of improving nurse-physician collaboration by enhancing organizational, professional, and interpersonal factors to form effective collaborative practice. Key words: nurse, physician, associated factors, collaboration