This paper describes a safety analysis of a transfer process for high-level radioactive and toxic waste. The analysis began with a hazard assessment that used elements of What If, Checklist, Failure Modes and Effects Analysis, and Hazards and Operability Study (HAZOP) techniques to identify and rough-in accident sequences. Based on this preliminary analysis, the most significant accident sequences were developed further using event trees. Quantitative frequency estimates for the accident sequences were based on operational data taken from the historical record of the site where the process is performed. Several modeling challenges were encountered in the course of the study. These included linked initiating and accident progression events, fire propagation modeling, accounting for administrative control violations, and handling mission-phase effects