Purpose: To assess the performance of adaptive optics scanning laser ophthalmoscopy (AOSLO) in a large sample of eyes with or without age-related macular degeneration (AMD) and with cataracts or intraocular lenses (IOLs). Methods: Patients with various degrees of AMD and age-similar normal subjects under-went fundus photography. Cataract severity and IOL clarity were assessed by fundus reflex photographs. In phakic eyes, lenticular opacity was graded as nuclear, cortical, or posterior subcapsular cataract. In eyes with IOLs, lens clarity was assessed by posterior capsule opacification (PCO). Quality of AOSLO images of the macular photoreceptor mosaicwasclassifiedasgood,adequateorinadequatebyhumangradersinasubjective assessment of cone visibility. Results: A total of 159 eyes in 80 subjects (41 males, 39 females, aged 72.5 ± 11.5 years, 16 normals) were examined. Seventy-nine eyes had IOLs, and 80 eyes were phakic. AOSLO produced good images in 91 eyes (57%), adequate images in eight eyes (5%), and inadequate images in 27 eyes (17%). AOSLO did not acquire images in 33 eyes (21%), because of dense lenticular opacity, widespread PCO, or problems specific to individual subjects. Conclusions: AOSLO images considered at least Adequate or better for visualizing cone photoreceptors were acquired from 62% of study eyes. Translational Relevance: AOSLO can be used as an additional imaging modality to investigate the structure of cone photoreceptors in research on visual function in AMD and in clinical trials involving older patients.