Introduction Informal caregivers, mostly family members or friends, have often been required to engage in medical/nursing tasks and to navigate complex healthcare systems. It is unclear whether those activities impact caregiver burden. Therefore, the purpose of this study was to examine predictive factors of caregiver burden in consideration of healthcare-related factors (caregivers' perception of performing medical/nursing tasks, care coordination, and number of hospitalizations). Methods Secondary analysis of cross-sectional survey data taken from the Caregiving in the U.S. 2015 was conducted. Data were collected by the National Alliance for Caregiving and the American Association of Retired Persons (AARP). Self-identified caregivers (n = 304) who provided care for individuals with cognitive impairment (ICI), and who were living in the community were participants in the study. Results The overall model explained 38.4% of the variance in caregiver burden (F = 20.48, p < 0.001). When examining each factor, perceived difficulty in medical/nursing tasks (beta = 0.38, p < 0.001) was the most influential factor, followed by caregivers' physical health (beta = -0.27, p < 0.001), income (beta = -0.13, p = 0.01), and level of the care coordination (beta = 0.12, p = 0.02). Discussion Although caregivers' involvement in healthcare-related activities for ICI is necessary, this involvement has a considerable impact on caregiver burden. Healthcare providers should be cognizant of caregiver burden related to healthcare-related activities. Moreover, researchers should develop interventions and community services to decrease caregivers' difficulty in performing their roles.