Older adults are vulnerable to drug overdose. We used a multi-method approach to prioritise risk factors for prescription drug overdose among older adults. The study was conducted in two stages. First, risk factors for drug overdose were classified according to importance and changeability through literature review, determined through 2-phase expert surveys. Second, prescription drug overdose cases during 2011–2015 were selected from a national cohort; the prevalence of ‘more important’ or ‘more changeable’ factors determined in stage one was investigated. Scores were assigned according to the Basic Priority Rating Scale formula, reflecting the problem size and seriousness and intervention effectiveness. In the first stage, polypharmacy, old-old age, female sex, chronic disease, psychiatric disease, and low socioeconomic status (SES) were selected as risk factors. In the second stage, 93.9% of cases enrolled had chronic medical disease; 78.3% were using multiple drugs. Low SES was more prevalent than other risk factors. As per the scoring formula, chronic medical disease, polypharmacy, psychiatric disease, low SES, female sex, and old-old age were the most important risk factors in order of priority. Patients with chronic medical disease and those using multiple medications should be prioritised in overdose prevention interventions among older adults.