This study compared the number and type of substances taken in deliberate self-poisoning with fatal (n = 127) and non-fatal (n = 521) outcome. The aims were (i) to describe substances typically involved in self-poisoning in England and Wales, (ii) to examine the role of drug "cocktails' and (iii) to examine whether toxic substances are over-represented in cases with fatal outcome. Over-the-counter (OTC) analgesics, minor tranquillizers and antidepressants accounted for about 70% of substances taken, irrespective of outcome. Compared with survivors, cases who died had taken a higher mean number of substances. Among self-poisonings with a single substance, antidepressants and paracetamol-opiate combinations were over-represented in fatal-outcome cases. This report emphasizes the role of OTC analgesics and antidepressants in overdose-related mortality in England and Wales.