Background.-Though symptomatic medication overuse is believed to play a major role in progression from episodic to chronic or transformed migraine (TM), population-based longitudinal data on these agents are limited.Objectives.-To assess the role of specific classes of acute medications in the development of TM in episodic migraine (EM) sufferers after adjusting for other risk factors for headache progression.Methods.-As a part of the American Migraine Prevalence and Prevention study (AMPP), we initially surveyed a population sample of 120,000 individuals to identify a sample of migraineurs to be followed annually over 5 years. Using logistic and linear regression, we modeled the probability Conclusion.-EM sufferers develop TM at the rate of 2.5% per year. Any use of barbiturates and opiates was associated with increased risk of TM after adjusting for covariates, while triptans were not. NSAIDs were protective or inducers depending on the headache frequency.