Exposures associated with common agricultural activities may increase risk of stroke. The authors evaluated associations between self-reported agricultural activities including pesticide use and handling of crops and stroke mortality among 51,603 male pesticide applicators enrolled in the Agricultural Health Study (AHS). Vital status was obtained through 2008. Stroke mortality was defined by underlying or contributing cause of death (ICD-9 430-438, ICD-10 I60-I69). Information regarding lifetime pesticide use, working with crops or animals, engagement in other agricultural activities, and potential confounders was self-reported at enrollment. Cox proportional hazards models, with age as the time scale, were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for state of residence, smoking status, and alcohol consumption. Median follow-up time was 13 yr, during which 308 stroke deaths occurred. No measure of overall or specific pesticide use was positively associated with mortality due to stroke. Stroke mortality was inversely associated with handling hay, grain, or silage at least once each year as reported at enrollment (HR: 0.75; 95% CI: 0.58, 0.98). There was no evidence of an association between pesticide use and stroke mortality. The inverse association between handling of hays and grains and stroke mortality may be due to (1) those engaging in such activities being healthier than those who did not or (2) exposure to some biological agent present in hays and grains. Further investigation of incident stroke, rather than stroke mortality, as well as stroke subtypes, is needed to determine the full role of agricultural exposures and stroke.