To evaluate the associations of presbyopia and its correction, particularly monovision optical correction, with vision-targeted health-related quality of life. The National Eye Institute Refractive Error Quality of Life (NEI-RQL) Instrument was prospectively self-administered by subjects from 6 medical centers in the following age and correction categories: subjects with emmetropia younger than 45 years (n = 75), subjects with emmetropia aged 45 years or older (n = 38), and subjects with ametropia aged 45 years or older without monovision (n = 486) or corrected with monovision (n = 38). Differences in the 13 NEI-RQL Instrument subscale scores among subjects in the 4 groups were examined. The age of 45 years or older was used as a surrogate for presbyopia. A comparison of older (age > or =45 years) vs younger (age <45 years) persons with emmetropia suggests that presbyopia was associated with reduced scores in 7 of 13 subscales (P<.05). In those aged 45 years or older, correction of presbyopia with monovision was associated with statistically significantly better scores on 3 subscales (expectations, dependence on correction, and appearance) compared with single-vision correction. One subscale (dependence on correction) showed worsening scores with increasing age without adjustment for need or type of correction. Older persons with monovision correction had significantly worse scores than younger subjects with emmetropia on all subscales except suboptimal correction and appearance. Presbyopia is associated with worse vision-targeted health-related quality of life compared with younger subjects with emmetropia. Monovision correction of presbyopia is related to some improvements in health-related quality of life, but it is still worse than that for younger subjects with emmetropia in several areas.