Background: Giving preventive therapy to children living in the households of TB patients to prevent them from developing TB themselves is important for reducing morbidity and mortality in this high-risk group. Children’s adherence to medications is likely dependent on their caregivers. We conducted a study to assess the association between caregivers’ knowledge and perceptions around isoniazid preventive therapy (IPT) and whether their children completed IPT. Methods: We conducted a retrospective medical record review of children who initiated IPT during 2017-2018 in 50 health facilities in south Lima, Peru. We administered structured surveys to caregivers of the children and about their knowledge and perceptions around IPT. To determine factors associated with IPT completion, we used a modified Poisson regression with generalized estimating equations to account for clustering by household. Results: We included in the study 550 children, of whom 31% did not complete IPT. Independent factors associated with not completing IPT were: low caregiver knowledge about TB and IPT (adjusted risk ratio [aRR]: 1.41; 95% confidence interval [CI]: 1.06-1.78), low caregiver perception of the importance of IPT (aRR: 1.76; 95% CI: 1.30-2.39), low caregiver satisfaction with the health services (aRR: 1.57; 95% CI: 1.14-2.16), experiencing adverse events (aRR: 2.08; 95% CI: 1.51-2.87), and living in a household with moderate or severe family dysfunction (aRR: 1.53; 95% CI: 1.07-2.19). Conclusions: IPT completion among children was associated with the knowledge and perceptions of their caregivers, as well as whether they experienced adverse events. To improve IPT completion among children, health care providers should prioritize education and counseling for caregivers, promote positive interpersonal relationships with them, and monitor adverse events.