Introduction: in resource-limited settings incorporating the Telemedicine system into the healthcare system enhances exchanging valid health information for practicing evidence-based medicine for the diagnosis, treatment, and prevention of diseases. The successful implementation of a telemedicine system in health care inquires a study of numerous technical, organizational, infrastructure, and human elements.Objective: This study aimed to assess health professionals' readiness and its associated factors to implement a Telemedicine system at private hospitals in Amhara Region, Ethiopia 2021.Method: An institution-based cross-sectional study was conducted among 423 health professionals from March 3 to April 7 2021 at private hospitals in Amhara Region. A self-administered questionnaire was employed to collect the data. The data were analyzed by SPSS version 20 software. Descriptive statistics,bi-variable and multi-variable logistic regression analyses were performed. An adjusted odds ratio (AOR) with 95% CI was used to determine the s association between the independent and the outcome variable. Result: About Two-third (268;65.4%) of health professionals were ready to Telemedicine system.Knowledge (AOR=2.5;95% CI: [1.4, 4.6]), Attitude (AOR=3.2;95% CI: [(1.6,6.2]), computer literacy (AOR=2.2; 95% CI: [1.3, 3.9]), computer training (AOR=2.1;95% CI: [1.1, 4.1]), Computer skill (AOR=1.9;95% CI:[1.1, 3.4]),computer access at office (AOR = 2.1;95% CI: [1.1,3.7],Internet access at office (AOR=2.8;95%CI: [1.6,5.1]),Own personal computer(AOR=3.0;95% CI: [1.5,5.9])and work experience(AOR=3.1;95%CI: [1.4,6.7]) were significantly associated withTelemedicine readiness .Conclusion and Recommendation: In general the overall readiness of health professionals for the Telemedicine system is moderate. Inclusive packages of capacity building are fundamental to increasing the level of, knowledge, attitude, and training among health professionals.