The needs of family caregivers providing care to relatives with visual impairment are often dismissed, leading to caregiver burden. The Zarit Burden Interview (ZBI) can measure the caregiver burden of caring for a family member with vision impairment. The purpose of this study is to validate the ZBI in Mexican family caregivers of patients with visual impairment. The ZBI was applied to 137 family caregivers of patients with visual acuity ≤ 20/200 in the best eye for ≥ 6months. The ZBI's reliability was determined using Cronbach's α and the factor structure using exploratory factor analysis (EFA, principal axis factoring with promax rotation). Items with loadings < 0.400 were eliminated. Retained factors were determined using the scree test and Horn's parallel analysis (95%CI). Associations between burden factors and other variables were evaluated with descriptive and inferential statistics. Mean ZBI score was 26.2 ± 13.1, and internal consistency was high (α = 0.871). EFA yielded four factors: (1) embarrassment and frustration, (2) self-efficacy expectations, (3) interference in personal relationships, and (4) personal strain. The α values ranged from 0.649 to 0.812. Spousal caregivers had significantly higher scores (factors 1, 2, and 4), whereas adult children had less scores (factor3). There was a significant positive correlation between hours of daily caregiving and factors 2 (r = 0.350) and 3 (r = 0.388). A worse degree of visual impairment was associated with higher mean factor scores in all factors. The ZBI is a valid instrument to detect burden in Mexican caregivers of patients with visual impairment. We identified a four-factor structure that improved our understanding of the ZBI's underlying constructs. Interventions targeting specific types of burden are warranted.