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Background: The measles Supplementary Immunization Activity (SIA) was implemented in June, 2017 to close immunity gaps by providing an additional opportunity to vaccinate children aged between 9 months and up to 14 years in Lilongwe District, Malawi. This study was conducted to determine the proportion of eligible children that were reached by the 2017 measles SIA among those children with or without history of measles vaccination, and possible reasons for non-vaccination., Methods: A cross-sectional survey using mixed methods was conducted. Caretakers of children who were eligible for the 2017 measles SIA were sampled from 19 households from each of the 25 clusters (villages) that were randomly selected in Lilongwe District. A child was taken to have been vaccinated if the caretaker was able to explain when and where the child was vaccinated. Eight Key Informant Interviews (KIIs) were conducted with planners and health care workers who were involved in the implementation of the 2017 measles SIA. Modified Poisson regression was used to examine the association between non-vaccination and child, caretaker and household related factors. A thematic analysis of transcripts from KIIs was also conducted to explore health system factors associated with non-vaccination of eligible children in this study., Results: A total of 476 children and their caretakers were surveyed. The median age of the children was 52.0 months. Overall, 41.2% [95% CI 36.8-45.7] of the children included in the study were not vaccinated during the SIA. Only 59.6% of children with previous measles doses received SIA dose; while 77% of those without previous measles vaccination were reached by the SIA. Low birth order, vaccination history under routine services, low level of education among caretakers, unemployment of the household head, younger household head, provision of insufficient information by health authorities about the SIA were significantly associated with non-vaccination among eligible children during the 2017 measles SIA. Qualitative findings revealed strong beliefs against vaccinations, wrong perceptions about the SIA (from caretakers' perspectives), poor delivery of health education, logistical and human resource challenges as possible reasons for non-vaccination., Conclusion: Many children (41%) were left unvaccinated during the SIA and several factors were found to be associated with this finding. The Lilongwe District Health Team should endeavor to optimize routine immunization program; and community mobilization should be intensified as part of SIA activities., Competing Interests: The authors have declared that no competing interests exist.