We investigated the drugs used in the alleviation of pain and symptoms (APS) with a possible life-shortening side effect in six European countries' end-of-life care. We sent mail questionnaires to physicians who signed a representative sample of death certificates in each country. APS with a possible life-shortening effect occurred from 19% of all deaths in Italy to 26% in Denmark. Physicians usually administered opioids (from 76% of APS cases in Italy to 96% in The Netherlands), but the type of opioids and administration practice differed markedly between countries. The doses of opioids given in the last 24 hours also varied significantly and were usually lower than 300 mg oral morphine equivalent (from 83% of cases in Belgium to 93% in Sweden). The highly variable results bring into question whether existing guidelines for pain relief were applied appropriately and to what extent unfounded concerns about the possible life-shortening effect of opioids resulted in less than optimal symptom management in end-of-life care.