The use of age-appropriate child restraint systems significantly reduces injury and death associated with motor vehicle crashes (MVCs). Pediatric obesity has become a global epidemic. Although recent evidence suggests a possible association between pediatric obesity and MVC-related injury, there are potential misclassifications of body mass index from under-estimated height in younger children. Given this limitation, age- and sex-specific weight percentiles can be used as a proxy of weight status. The specific aim of this study was to determine the association between weight percentile and the risk of significant injury for children 3-8 years in MVCs. This was a cross-sectional study of children aged 3-8 years in MVCs in 16 US states, with data collected via insurance claims records and a telephone survey from 12/1/98-11/30/07. Parent-reported injuries with an abbreviated Injury Scale (AIS) score of 2+ indicated a clinically significant injury. Age- and sex-specific weight percentiles were calculated using pediatric norms. The study sample included 9,327 children aged 3-8 years (weighted to represent 157,878 children), of which 0.96% sustained clinically significant injuries. There was no association between weight percentiles and overall injury when adjusting for restraint type (p=0.71). However, increasing weight percentiles were associated with lower extremity injuries at a level that approached significance (p=0.053). Further research is necessary to describe mechanisms for weight-related differences in injury risk. Parents should continue to properly restrain their children in accordance with published guidelines.