Introduction: Mental distress is a mental or psychological syndrome, which influences thernhealth status and treatment effectiveness, getting quality of care in a hospitalized medicalrnsurgical inpatients. It is more common in hospital setting than community setting population. rnObjective: To assess the prevalence of mental distress and associated factors amongrnhospitalized medical surgical adult inpatients in public hospitals, Addis Ababa, Ethiopia, 2020. rnMethods: Institutional based cross sectional study was conducted with a total of 408 studyrnsubjects from March 1-30, 2020. Systematic random sampling technique was used and data wasrncollected using interviewer administered questionnaire. Data was collected by trained nursingrnstudents, collected data was entered into Epi-data 3.1 and export to SPSS version 26 for analysis,rnand then binary and multiple logistic regression was performed to check the association betweenrndependent and independent variable. rnResult: The prevalence of mental distress among hospitalized medical surgical adult inpatientsrnin public hospitals was 53.1% with (95%CI; 48%, 58%). Variables of being marriedrn[AOR=2.67; 95%CI(1.065,6.683)], private employee [AOR=2.21; 95%CI (1.001, 4.900)], dailyrnlaborer [AOR=4.70; 95%CI(1.218,18.215)], rural residence [AOR=1.85; 95%CI(1.047,3.264)],rntaking alcohol [AOR=1.68; 95%CI(1.025, 2.740)], previous psychiatric illness[AOR=3.40;rn95%CI(1.078, 10.737)] and comorbidity [AOR=1.93; 95%CI (1.200, 3.094)] were found to bernsignificantly associated with mental distress; while age, sex, ethnicity, religion, educationalrnstatus, income, smoking, chat, social support, living condition, history of hospitalization, wardrnadmitted and length of hospital stay were not significantly associated. rnConclusion and recommendation: The prevalence of mental distress was high and beingrnmarried, private employee, daily laborer, residence in rural area, previous history of psychiatricrnillness, alcohol used and comorbidity disorder were associated with mental distress amongrnhospitalized adult inpatients, there for health care providers should provide special considerationrnto those group of patients admitted to the hospital.