This systematic review was conducted to determine the effect of periodic motor vehicle inspections on road crashes and injuries, compared to less exposure to periodic inspections or no inspections. The Medline, Web of Science, and Scopus databases were used to search the literature. Ecological studies were specifically excluded. A reverse search of the results with these databases and of other identified narrative reviews was also performed. Of the 5065 unique references initially extracted, only six of them met the inclusion criteria and were selected for review: one experimental study, two cohort studies with an internal comparison group, two cohort studies without a comparison group, and one case–control study. Two authors independently extracted the information and assessed the quality of each study. Due to the heterogeneity of the designs and the intervention or comparison groups used, quantitative synthesis of the results was not attempted. Except for the case–control study, which showed a significant association between road crashes and the absence of a valid vehicle inspection certificate, the other studies showed either a small reduction in crash rates (around 9%), no association, or a higher crash rate in vehicles with more inspections. In all observational studies, the risk of residual confounding bias was significant and could have explained the results. Therefore, although the research reviewed here suggests that periodic inspection may be associated with a slight reduction in road crashes, the marked heterogeneity along with probable residual confounding in most reports prevented us from establishing causality for this association.