Catastrophic health expenditure (CHE) is an indicator used by the World Health Organization (WHO) to assess equity in households' payments to the health system. In this paper, we prospectively calculated the population at risk of facing catastrophic expenditure due to purchasing three selected medicines (metformin, atorvastatin and amoxicillin) in Iran.This study draws on the data set of the Iranian National Household Survey of 38244 households in Iran. CHE was calculated based on "capacity to pay" using different thresholds.20, 16 and 3 households had to spend more than 40% of their capacity to pay on amoxicillin, atorvastatin and metformin respectively. Lowest priced generic (LPG) medicines were found more affordable than the original brand (OB) medicines. Age, literacy and gender of head of household, economic status, settlement, size and number of breadwinners in the households share important association with CHE.Requirement of these specific medicines for long-term may subject the Iranian households to CHE. The study demonstrates important and specific insights for health policy makers in Iran to protect the households from healthcare catastrophes.