OBJECTIVE: To examine the characteristics of seizure-related vehicle crashes (SRC). METHOD: Using a nested case-control design, we identified and compared cases of SRC involving confirmed epilepsy patients with 137,126 non-seizure-related crash controls (NSRC) in the Australian state of Victoria. SRC were identified from approximately 20,000 epileptologist medical records by cross-referencing this source with the Victorian Police Traffic Incident database and the Road Crash Information System Database (RCISD). RESULTS: Seventy-one SRC involving 62 patients with epilepsy were identified. Thirty-seven SRC resulted in injury and could be identified in the RCISD and compared to NSRC. Seizure-related crashes typically involved a single vehicle (57% vs 29%, p < 0.001) carrying a sole occupant (95% vs 48%, p = 0.001). Most SRC began with an "out of control movement" (51% vs 10%, p < 0.001) and the subsequent collision type differed significantly between the groups (p < 0.001). The majority of SRC were a "collision with a fixed object" (54% vs 17%, p < 0.001) involving an "off path on straight" mechanism (48% vs 10%, p < 0.001). Regarding all 71 SRC, generalized as compared with focal epilepsy crashes involved younger drivers (p < 0.001), seizure-provoking factors (p = 0.033), and occurred earlier in the day (p = 0.004). CONCLUSIONS: Given the distinct SRC features, we propose that clinicians, crash investigators, and driver licensing authorities incorporate collision characteristics into the overall assessment of suspected SRC. Further research should examine restricting driving immediately after risk periods as a harm-minimization strategy.