A total of 137 urine samples and 46 serum samples, corresponding to 154 self-confessed designer drugs consumers in Ibiza island, were analyzed for the presence of designer drugs: amphetamine and amphetamine derivatives (methamphetamine, methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), methylenedioxyamphetamine (MDA), p-methoxymethylamphetamine (PMMA), p-methoxyamphetamine (PMA), etc.), ketamine and gamma-hydroxybutyric acid. Among this population, coming both from the forensic clinic and from the emergency room of a hospital, a total of 99 cases were found positive for some designer drug. This study shows the prevalence of methylenedioxymethamphetamine (MDMA) among designer drug users, sole or in association with other drugs. Also, the mixture of MDMA with other designer drugs, ethanol and/or cocaine is shown to be more likely to produce toxic symptoms requiring clinical attendance in a hospital emergency room. These findings along with the consumption history, the concentrations of drugs and metabolites in urine and serum and the toxicological significance for the interpretation of some MDMA metabolites such as 4-hydroxy-3-methoxymethamphetamine (HMMA) are discussed in this study.