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Background: The prevention of child mortality through immunization is one of the most cost-effective and widely applied public health interventions. In Ethiopia, the Expanded Program on Immunization (EPI) schedule is rarely completed as planned and the full immunization rate is only 24%. The objective of this study was to identify determinant factors of incomplete childhood immunization in Arbegona district, Sidama zone, southern Ethiopia.Methods: A community based unmatched case-control study was undertaken among randomly selected children aged 12 to 23 months and with a total sample size of 548 (183 cases and 365 controls). A multi-stage sampling technique was used to get representative cases and controls. Data was collected using a structured questionnaire and analyzed using SPSS version 16 statistical software. Bivariate and multiple logistic regression analyses were done to identify independent factors for incomplete immunization status of children. Qualitative data were also generated and analyzed using thematic framework.Results: The incomplete immunization status of children was significantly associated with young mothers (AOR = 9.54; 95% CI = 5.03, 18.09), being born second to fourth (AOR = 3.64; 95% CI = 1.63, 8.14) and being born fifth or later in the family (AOR = 5.27; 95% CI = 2.20, 12.64) as compared to being born first, a mother's lack of knowledge about immunization benefits (AOR = 5.51; 95% CI = 1.52, 19.94) and a mother's negative perception of vaccine side effects (AOR = 1.92; 95% CI = 1.01, 3.70). The qualitative finding revealed that the migration of mothers and unavailability of vaccines on appointed immunization dates were the major reasons for partial immunization of children.Conclusion: To reduce the number of children with incomplete immunization status, the Arbegona district needs to consider specific planning for mothers with these risk profiles. A focus on strengthening health communication activities to raise immunization awareness and address concerns of vaccine side effects at community level is also needed. This could be achieved through integrating the immunization service to other elements of primary health care. [ABSTRACT FROM AUTHOR]