Murders committed by juveniles remain a serious concern in the United States. Most studies on juvenile homicide offenders (JHOs) have used small samples and have concentrated on male offenders. As a result, little is known about female JHOs and how they differ from their male counterparts on a national level. This study utilized the Supplementary Homicide Report (SHR) database to examine more than 40,000 murders committed by male and female juvenile offenders from 1976 to 2005. This research effort, the most expansive to date, replicated previous findings with respect to gender differences using bivariate and multivariate analyses. As predicted, six variables used to test eight hypotheses with respect to male and female JHOs in single-victim incidents were significant (victim age, victim–offender relationship, murder weapon, offender count, victim gender, and homicide circumstance). Regression analysis revealed that all variables remained significant when entered into the model. This article concludes with a discussion of our findings and directions for future research.