BACKGROUND: Higher BMI in middle age is associated with ischemic stroke, but little is known about BMI over adulthood, and the risk for ischemic stroke as most studies relied on a single measurement of BMI. METHODS: BMI was measured four times over a period of 42 years. We calculated average BMI values and group-based trajectory models and related these to the prospective risk of ischemic stroke after the last examination in Cox models with a follow-up time of 12 years. RESULTS: A total of 14,139 participants, with a mean age of 65.2 years and 55.4% women, had information on BMI from all four examinations, and we observed 856 ischemic strokes. People with overweight and obesity over adulthood had a higher risk for ischemic stroke with a multivariable-adjusted hazard ratio of 1.29 (95% CI 1.11-1.48) and 1.27 (95% CI 0.96-1.67), respectively, when compared to normal weight participants. Excess weight tended to have stronger effects earlier than later in life. A trajectory of developing obesity throughout life was associated with higher risk than other trajectories. CONCLUSIONS: High average BMI, especially at an early age, is a risk factor for ischemic stroke. Early weight control and long-term weight reduction for those with high BMI may decrease the later occurrence of ischemic stroke.