Background: Adults aged 85 and older, often referred to as the oldest-old, are the fastest growing segment of the population. The rapidly increasing number of older adults with chronic and multiple medical conditions poses challenges regarding their driving safety. Objective: To investigate the effect of advanced age on driving safety in drivers with medical conditions. Methods: We categorized 3,425 drivers with pre-existing medical conditions into four age groups: middle-aged (55-64, n = 1,386), young-old (65-74, n = 1,013), old-old (75-84, n = 803), or oldest-old (85+, n = 223). All underwent a formal driving evaluation. The outcome measures included fitness-to-drive recommendation by the referring physician, comprehensive fitness-to-drive decision from an official driving evaluation center, history of motor vehicle crashes (MVCs), and history of traffic violations. Results: The oldest-old reported more cardiopulmonary and visual conditions, but reported less neurological conditions than the old-old. Compared with the middle-aged, the oldest-old were more likely to be considered unfit-to-drive by the referring physicians (odds ratio (OR) = 4.47, 95% confidence interval (CI) 2.20-9.10) and by the official driving evaluation center (OR = 2.74, 95% CI 1.87-4.03). The oldest-old reported more MVCs (OR = 2.79, 95% CI 1.88-4.12) compared to the middle-aged. Conclusion: Advanced age adversely affected driving safety outcomes. The oldest-old are a unique age group with common medical conditions known to interfere with safe driving. Driving safety strategies should particularly target the oldest-old since they are the fastest growing group and their increased frailty is associated with severe or fatal injuries due to MVCs.