At the beginning of each month, there is a spike in government payments to individuals, resulting in a beginning-of-the-month spike in purchases of prescription drugs and in increased pharmacy workloads. Studies suggest that pharmacy error rates increase with increased workloads. These facts raise an important and previously unanswered question: is there a spike in fatal medication errors at the beginning of each month? We examined all United States death certificates from 1979-2000 (> 47,000,000 deaths) and showed that medication error deaths for which the decedent was dead on arrival or died in the emergency room or as an outpatient spiked by 25% above normal at the beginning of each month. This beginning-of-the-month spike (25% +/- 4%) was larger than for any other major cause of death. The beginning-of-the-month spike did not vary by socioeconomic status and was not larger for substance abusers than for others. Five explanations for the findings were tested. Evidence suggested that the spike in medication error deaths cannot be solely attributed to a spike in the consumption of alcohol or drugs. An increase in pharmacy error rates might play a role.