Pregnancy causes diverse physiologic and lifestyle changes that may contribute to increased driving and driving error. We compared the risk of a serious motor vehicle crash during the second trimester to the baseline risk before pregnancy.We conducted a population-based self-matched longitudinal cohort analysis of women who gave birth in Ontario between April 1, 2006, and March 31, 2011. We excluded women less than age 18 years, those living outside Ontario, those who lacked a valid health card identifier under universal insurance, and those under the care of a midwife. The primary outcome was a motor vehicle crash resulting in a visit to an emergency department.A total of 507,262 women gave birth during the study period. These women accounted for 6922 motor vehicle crashes as drivers during the 3-year baseline interval (177 per mo) and 757 motor vehicle crashes as drivers during the second trimester (252 per mo), equivalent to a 42% relative increase (95% confidence interval 32%-53%; p<0.001). The increased risk extended to diverse populations, varied obstetrical cases and different crash characteristics. The increased risk was largest in the early second trimester and compensated for by the third trimester. No similar increase was observed in crashes as passengers or pedestrians, cases of intentional injury or inadvertent falls, or self-reported risky behaviours.Pregnancy is associated with a substantial risk of a serious motor vehicle crash during the second trimester. This risk merits attention for prenatal care.