Introduction: - Rifampicin-resistant tuberculosis is caused by bacteria that do not respond to rifampicin. The emergence and spreading of Rifampicin-resistance strains of mycobacterium tuberculosis poses significant challenges to tuberculosis control programs particularly in resource-limited countries like Ethiopia. In Eastern part of Amhara Region rifampicin-resistance also a major challenge for TB control and the available study doesn’t show proportion and factor associated with rifampicin-resistance among new pulmonary tuberculosis patients. Objective: - The aim of this study was to assess proportion and factors associated to rifampicin resistance among new pulmonary tuberculosis patients in Eastern part of Amhara Region, Ethiopia, 2019. Methods: - A facility based cross-sectional study design was conducted among 570 new pulmonary tuberculosis patients in Eastern Part of Amhara Region, Ethiopia from April to November, 2019. Systematic random sampling technique was used to select the study participants from 8 stratified Gene-Xpert site hospitals. Structured questionnaire and document reviews were used to collect data. Rifampicin resistance was detected by rapid Gene-Xpert assay from sputum specimens. Variables with P-value <0.2 in simple binary logistic regression were included in the multiple binary logistic regressions. Statistical test was reported as significant when p-value < 0.05 in multiple variable logistic regressions. Fitness of goodness was checked by using Hosmer Lemeshow model fitness test. Results:-A total of 570 new pulmonary tuberculosis patients were participated in this study. Of those, 43 (7.50%) 95% CI: 5-10) was resistance to rifampicin. Persons have contact history with known tuberculosis Patients (AOR 2.5 [95% CI: 1.21-5.11]), persons with human immune virus infection (AOR 2.3 [95% CI: 1.11-4.73]) and persons being diabetic mellitus cases (AOR 4.2[95% CI: 1.51-8.78]) were factors significantly associated with rifampicin resistance. Conclusions and recommendations: - Proportion of rifampicin resistance among new tuberculosis patients was high. Identified factors significantly associated with rifampicin resistance were: - Persons, who have contact history with known tuberculosis patients, have human immune virus infection and being diabetic mellitus cases. Strengthen prevention of rifampicin resistance tuberculosis transmition, strengthening contact tracing, improve tuberculosis-human immune virus health care services, and screening tuberculosis patient for diabetic mellitus are crucial. Keywords:-Tuberculosis, Rifampicin resistance, Gene-Xpert, Eastern Amhara, Ethiopia.