Background <p>Age-related macular degeneration (AMD) is a leading cause of visual impairment in older adults. Given the high prevalence of polypharmacy in this population, cumulative medication effects, particularly anticholinergic burden, may represent a clinically relevant factor requiring further investigation. This study aimed to investigate the association between anticholinergic burden, overall drug burden, and geographic atrophy secondary age-related macular degeneration (GA secondary to AMD).</p> Methods <p>In this case-control study, 102 participants aged 55–90 years were included. Anticholinergic burden was assessed using the Anticholinergic Cognitive Burden (ACB) scale. Medications regularly used by patients for chronic conditions and continued for a minimum duration of three months were included. Drug burden was defined as polypharmacy (≥ 5 medications). Multivariate logistic regression analyses were performed adjusting for age, gender, and multimorbidity.</p> Results <p>Patients with GA secondary to AMD had a higher number of medications and a greater prevalence of both drug burden and anticholinergic burden compared to controls (<i>p</i> = 0.010, <i>p</i> = 0.039, and <i>p</i> = 0.046, respectively). In multivariate analysis, anticholinergic burden (OR: 2.55, 95% CI: 1.11–5.84, <i>p</i> = 0.026) and drug burden (OR: 3.41, 95% CI: 1.21–9.58, <i>p</i> = 0.017) were independently associated with GA secondary to AMD.</p> Conclusions <p>Increased anticholinergic and overall drug burden were independently associated with GA secondary to AMD in older adults. These findings suggest a potential relationship between cumulative medication exposure and AMD. Further prospective studies are needed to determine whether this association has clinical or causal significance.</p>