OBJECTIVE: To investigate the association between age-related macular degeneration (AMD) and exposure to antacids, antithyroids, thyroid hormones, and thiazide diuretics. DESIGN: Matched case-control study. PARTICIPANTS: Population-based participants were selected from the United Kingdom General Practice Research Database. A total of 18,007 people with diagnosed AMD were compared with 86 169 controls matched for age, gender, and general practice. METHODS: Conditional logistic regression was used to determine the association between exposure to each drug group of interest and a diagnosis of AMD, adjusting for relevant confounding variables. MAIN OUTCOME MEASURES: The primary outcome was the odds ratio for the association between exposure to antacids, antithyroids, thyroid hormones, or thiazide diuretics and AMD. Secondary analyses were conducted to assess the effect of recent exposure to the drugs of interest, the total number of prescriptions received, and restricting the data set to participants with more than 2 years of observation time. RESULTS: The crude odds ratios for association between any record of drug exposure and AMD were as follows: 1.34 (95% confidence interval [CI], 1.29-1.39) for antacids; 1.15 (95% CI, 0.92-1.44) for antithyroids; 1.34 (95% CI, 1.29-1.39) for thyroid hormones; and 1.13 (95% CI, 1.08-1.17) for thiazide diuretics. After adjusting for consultation rate, observation time, diabetes, heart failure, hyperlipidemia, cardiovascular drug use, atherosclerosis, hypertension, aspirin use, hormone replacement therapy use, body mass index, alcohol consumption, and smoking, the odds ratios reduced to: 1.06 (95% CI, 1.02-1.10) for antacids, 0.98 (95% CI, 0.78-1.24) for antithyroids, 0.99 (95% CI, 0.92-1.06) for thyroid hormones, and 0.98 (95% CI, 0.94-1.02) for thiazides. Secondary analyses were consistent with these findings for all 4 drug categories. CONCLUSIONS: No association was detected between short- and medium-term use of antithyroids, thyroid hormones, and thiazide diuretics and the risk of AMD. Short- and medium-term use of antacids seems to be associated with a small increase in the risk of this disease. However, this increased risk is likely the result of residual confounding by smoking or uncontrolled confounding resulting from socioeconomic status. No conclusions could be drawn regarding longer-term use of each drug category.