Few studies have examined the effectiveness of low vision rehabilitation for age-related maculopathy (ARM) patients and its impact on vision-specific health-related quality of life (HRQoL). However, before a multi-site clinical trial can be conducted, appropriate outcome measures need to be identified for ARM patients who seek out low vision rehabilitation, including a vision-specific HR QoL instrument. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was developed to assess vision-specific HRQoL for low vision patients, including those with ARM. This study examines the performance of the NEI VFQ-25 among ARM patients who seek out low vision services and examines its relationship with visual acuity and self-reported use of low vision aids. One hundred and twenty-seven patients were recruited from a University-affiliated low vision clinic. During two telephone interviews, subjects completed the NEI VFQ-25 and a short cognitive test and provided information on general health and use of low vision aids. Additional information on visual acuity and eye health were collected from the medical record. Our results indicate that ARM patients who seek out low vision services report significant impairment in their vision-specific HRQoL. Their NEI VFQ-25 scores were lower compared to other ARM and low vision rehabilitation samples previously studied. The VFQ subscales with the largest deficits were near and distance visual acuities and psychosocial issues (near vision, distance vision, role difficulties, dependency, social functioning, mental health). These subscale scores were lower for those with greater visual acuity impairment. The VFQ subscale scores most impacted by the disease had wide variability and were higher for those who used low vision aids, suggesting that the NEI VFQ-25 is suitable for measuring further decline and treatment-related improvements. Thus, it should be strongly considered for a multi-site clinical trial on the effectiveness of low vision rehabilitation.