Background: Depression is a mental disorder that presents with a depressed mood, loss of pleasure or interest, decrease in energy, feeling of guilt or low self-worth, disturbed sleep, loss of appetite, and poor-concentration. Healthcare professionals are more susceptible to depression because they face higher amounts of professional stress in their job and academic lives. However, there is limited knowledge regarding health professionals’ level of depressive disorder in Ethiopia. This study aimed to assess the prevalence of depression and associated factors among health professionals, at Saint Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia. Methods: We conducted an institution-based cross-sectional study among 439 randomly selected health care worker using interviewer-administered patient health questionnaire-9 from April to May 2023. Ordinal logistic regression was performed to identify predictors of depressive disorder. Result : The overall prevalence of depressive symptoms among health care workers was 56.5% (95% CI (51.8% ,61.1%)). There were reports of mild (35%), moderate (13%) and severe (9%) depression, respectively. Marital status of being single (AOR=7.78, 95%CI: 1.123, 49.01), history of childhood abuse (AOR=2.57, 95%CI:1.49, 4.42), history of suicidal attempt (AOR=2.66, 95%CI:1.25,5.67), having history of stressful life event (AOR=1.527, 95%CI: 1.02,2.3), back pain over the past 30 days (AOR=2, 95%CI: 1.30,3.11), working for more than 8 hours (AOR=3.03, 95%CI: 1.12,8.24), and having experience of 5-10 year (AOR=4, 95%CI: 1.05,15.27) and 10-15 years (AOR= 4.24, 95%CI: 1.08,16.58) and poor social support (AOR= 2.09, 95%CI: 1.09,3.99) were statistically associated with increased level of depressive disorder. Conclusion : Healthcare professionals’ higher rate of depression was due to the higher work load, childhood abuse, history of stressful life, back pain, and poor social support. Thus, the hospital or ministry of health should give special attention to health care workers who has high work load, childhood abuse, history of stressful life, back pain, and poor social support to reduce the burden of depressive disorder among health professionals. Furthermore, early depression screening and treatment in hospitals is needed.