A retrospective population-based case-control study was conducted to determine whether driver sleepiness/fatigue and inattention/distraction increase the likelihood that a commercial motor vehicle collision (CVC) will be fatal. Cases were identified as CVC drivers who died (fatal) and controls were drivers who survived (nonfatal) an injury collision using the Kentucky Collision Report Analysis for Safer Highways (CRASH) electronic database from 1998-2002. Cases and controls were matched on unit type and roadway type. Conditional logistic regression was performed. Driver sleepiness/fatigue, distraction/inattention, age of 51 years of age and older, and nonuse of safety belts increase the odds that a CVC will be fatal. Primary safety belt law enactment and enforcement for all states, commercial vehicle driver education addressing fatigue and distraction and other approaches including decreased hours-of-service, rest breaks and policy changes, etc. may decrease the probability that a CVC will be fatal.