Abuse of prescription and illicit drugs has been rapidly increasing. This study examines the prevalence of drug use in the non-natural deaths of pregnant or recently pregnant women. Records from Florida's Pregnancy Associated Mortality Review conducted between 1999 and 2005 (n = 415) were linked to 385 toxicology reports obtained from Florida medical examiners' offices. The final study sample consisted of 169 drug-positive, pregnancy-associated non-natural deaths. Of these, 86 were positive for both blood and urine, 64 were positive for blood only and five for urine only, and the remainder were positive for some other specimen. Among these deaths, 91 cases (54%) involved prescription drugs, 78 cases (46%) involved illicit drugs, and 69 cases (41%) involved alcohol. Opioids constituted the majority of deaths associated with prescription drugs. Substantial co-use of opioids and benzodiazepines was seen. Pregnant or recently pregnant women may have more interactions with healthcare providers, which may present more opportunities for intervention and prevention.