Introduction Loss to follow-up (LTFU) is a critical factor in determining clinical outcome in HIV treatment programs. Identifying modifiable factors of LTFU is fundamental for designing effective patient retention interventions. We analysed factors contributing to children LTFU from a treatment program to identify those that can be modified. Methods A case-control study involving 313 children was used to compare the sociodemographic and clinical characteristics of children LTFU (cases) with those remaining in care (controls) at a large paediatric HIV care setting in Botswana. We traced children through caregiver contacts and those we found, we conducted structured interviews with the patients’ caregivers. Results Children Conclusion Paediatric patients and their caregivers need to be targeted and engaged at their initial clinic visit, with special attention to children Disclosure of interest statement Funding for this study was made possible through Fogarty International Centre of the National Institutes of Health, (M. W. Kline – Principal Investigator) under grant number D43 TW01036.