Objectives. The objective of this review was to assess the risk of obesity in injuries and fatalities resulting from motor vehicle crash (MVC), as compared with individuals with a normal-range body mass index. Methods. A systematic review of the literature was conducted yielding 824 potential studies. Nine of these studies met our inclusion criteria. Meta-analyses examining obesity as a risk factor for various injury types and risk of fatality were conducted using data from these studies. Results. Obesity was associated with higher fatality risk (odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.51-2.37, P = .0001; pooled estimate from 6 studies), and increased risk of lower extremity fractures (OR = 1.39, 95% CI = 1.18-1.65, P = .0001; pooled estimate from 2 studies). No significant differences were observed when considering abdominal injuries or pelvic fractures. Interestingly, for head injuries obesity was a protective factor (OR = 0.67, 95% CI = 0.46-0.97, P = .0001; pooled data from 3 studies). Conclusions. Evidence strongly supports the association of obesity with higher fatality and fractures of the lower extremities in MVCs. Contrary to our hypothesis, 3 studies showed that obesity was a protective factor in reducing head injuries. Furthermore, the review shows that obesity was not a risk factor of MVC-related pelvic fractures and abdominal injuries.