Introduction A significant number of nurses is leaving the health care sector. High rates of turnovers contribute to labor shortages of nursing and adversely affect patient outputs and nursing costs.Objectives To determine the magnitude of nurses’ intention to leave a job and its associated factors.Methods A cross-sectional, analytical descriptive study design among 634 nurses working in Tigray Regional State general hospitals from March 2018 to 30 June 2019 was conducted. Clustered random sample nurses completed self-administered three-item Michigan Organizational Assessment Questionnaire during data collection. Descriptive and multiple logistic regression analyses were done using SPSS version 20, 95% confidence interval and p-value < 0.05 was considered.Findings Response rate was 95.9%. Nurses were with a mean of 33.60 ± 9.71, 10.07 ± 9.54, and 2.10 ± 1.455 in years for age, work experience, and service in hospital respectively. About 56.4% were females, 95.4% Orthodox, and 56.7% were Bachelors of Science in Nursing. The magnitude of nurses’ intention to leave their jobs was 43.9%. The male nurses were 1.5 times more likely (AOR = 1.565, 95% CI = 1.095–2.237) had the intention to leave. Those nurses working in medical ward were also 2 times more likely (AOR = 1.886, 95% CI = 1.113–3.193) than working in the Out-Patient Department of the hospitals had the intention to leave.Conclusions Nurses in hospitals intend to leave their jobs. Gender and working in medical ward are the predictors for their intentions. Health care policymakers are recommended to develop nurses’ retention strategies and establish continuing education to socialize male nurses and set economic incentive strategies to encourage male nurses to stay in hospitals fulfilling their families’ income to earn. Managers are recommended to make regular rotation of nurses within hospitals to minimize a possible burden in medical wards. For the quality nursing care, nursing managers should create a favorable environment in medical wards. Educators are recommended to increase the intake of the nursing students. This study did not show the cause and effect of variables. Therefore, other researchers are recommended to conducting longitudinal studies.