Background: The Corona virus disease 2019 (COVID-19) vaccine acceptance was lower in developing countries and it varies from place to place and between population groups. There is limited evidence of vaccine acceptance and associated factors among chronic patients. Objective: To assess magnitude of COVID 19 vaccine acceptanceand associated factors among chronic patients at Wachamo University Nigist Eleni Mohammed comprehensive specialized hospital, southern Ethiopia, 2022. Method: A facility based mixed approach (quantitative study complemented by qualitative study) was conducted from March 20 to April 20, 2022. For quantitative study 371 participants were selected by simple random sampling and 14 participants were purposively selected for qualitative study. Binary logistic regression model was used to determine the association between independent and dependent variable. Crude and adjusted odds ratio with 95% confidence interval was computed and a variable with p-value < 0.05 was considered statistically significance. Qualitative data were transcribed verbatim then translated to English and thematic analysis was usedsupported by ATLAS ti.version 22. Finally the finding was triangulated at interpretation. Result: Of the 371 participants, 319(85.98%) respondents were willing to take the vaccine at any time. Knew someone diagnosed with COVID 19 [AOR 4.03; 95% CI (1.73, 9.41)], having good knowledge [AOR 3.2; 95% CI (1.40, 7.32)], favorable attitude towards to COVID 19 vaccine [AOR 2.48; 95% CI (1.12, 5.47)] and completed secondary and above educational status [AOR 4.38; 956% CI (1.17, 16.44)] were statistically associated variables with vaccine acceptance. Conclusion: The magnitude of COVID 19 vaccine acceptance was higher. Knew someone diagnosed with COVID 19 infection, having good knowledge, favorable attitude and completed secondary education were significantlyassociated withCOVID 19 vaccine acceptance. However, strengthening continuous health education and promotion about the vaccine is still crucial to avoid unwanted rumors which leadsvaccine refusal.