Limited contemporary data are available describing the incidence rates, hospital prognosis, and factors associated with the occurrence of ventricular fibrillation (VF) in patients hospitalized with acute myocardial infarction (AMI). The objectives of our study were to examine 3-decade-long trends (1975 to 2005) in the magnitude, predictors, and hospital case-fatality rates associated with VF in residents of a large New England metropolitan area hospitalized at all area medical centers with an uncomplicated AMI. The study population consisted of 7,472 residents of the Worcester (Massachusetts) metropolitan area hospitalized with an uncomplicated AMI in 15 annual periods from 1975 to 2005. The overall proportion of patients who developed VF was 4.2%. The incidence rates of VF remained stable from 1975 to 1995 but decreased thereafter, reaching their lowest frequency in 2005 (1.9%). Hospital case-fatality rates were significantly higher in patients with (40.9%) compared with those without (2.5%) VF. Decreases in hospital death rates over time were observed in patients with and without VF, with the decreases in death rates being greater for patients with VF. Patients who developed a Q-wave MI or a left or right bundle branch block were at particularly increased risk for developing VF. In conclusion, our results indicate that the incidence and hospital death rates associated with VF have decreased during recent years.