Healthcare is crucial service industry that has significant effects for facilitating productivityrnincreases, supporting the populationâ€™s general wellbeing and enabling them to pursue a morernmeaningful life. Every healthcare institute is expected by the public to render quality andrnprofessional healthcare services. In order to do so, healthcare institutes need employees to bernsatisfied with their jobs. This study was designed to examine determinant factors of jobrnsatisfaction among health professionals in Ayder referral hospital, Mekelle, Tigray, Ethiopia. Arncross-sectional study was conducted to determine the level and factors affecting job satisfactionrnof health professionals working in Ayder referral hospital. It was conducted from February tornMay and included all categories of health professionals working in the hospital during the studyrnperiod. Data was collected using both qualitative and quantitative data collection methods. Afterrnthe data was collected, it was feed on to excel and analyzed using SPSS version 20.0. Descriptivernstatistics, bivariate and multivariate logistic regression analysis were used to identify associatedrnfactors with job satisfaction and P-value < 0.05, at 95% CI was taken as cut off point forrnstatistical significance. A total of 223 health professionals have responded for the selfrnadministered questionnaire. The result showed that 123 (55.2%) of the respondents wererndissatisfied with their job. The major reasons reported for their dissatisfaction were lack ofrncompensation & benefits, inadequate promotion, recognition, feedback, poor leadership practicernand low salary. 91 (40.8%) health professionals were satisfied with interpersonal relationship,rnachievement, autonomy, work itself and working conditions subscales. Particularly, Participant'srnresponses indicated that autonomy, work itself, salary, interpersonal relationships, leadership,rncompensation & benefits and working conditions subscales were the final predictors of overallrnjob satisfaction. Job satisfaction of health professionals in Ayder referral hospital was found tornbe low. Responsible bodies should formulate mechanisms to improve job satisfaction of healthrnprofessionals so as to improve the healthcare services of the hospital.