Objective To investigate the medication adherence to antihypertensives, antidiabetics, and lipid-lowering agents and its influence on the prognosis of individuals at high risk of stroke. Methods A total of 16892 residents aged 40 years or above in eight communities in Sichuan participated in a face-to-face study from May to September 2015. A database of a high-risk population of stroke in Sichuan province was established, and data were collected via using a standardized structured questionnaire by experienced investigators, including the treatment status and medication compliance of participants with hypertension, diabetes, or dyslipidemia during the follow-up period. Multiple logistic regression analyses were performed to explore the influencing factors of medication adherence and its influence on the prognosis of individuals at high risk of stroke. Results A total of 2893 participants at high risk of stroke were enrolled. The treatment rates of hypertension, diabetes, and dyslipidemia were 50.1%, 49.2%, and 5.1%, respectively, when the high-risk individuals were identified. At the end of follow-up (with a median follow-up period of 4.8 years), the treatment rates of hypertension, diabetes, and dyslipidemia were 24.8%, 25.0%, and 7.9%, respectively. Medication adherence to antihypertensives, antidiabetics, and lipid-lowering agents were 27.8%, 25.5%, and 18.1%, respectively. Multiple logistic regression analyses showed that the education level of high school or above [odds ratio (OR)=2.134, 95% confidence interval (CI) (1.098, 4.147), P=0.025], medical insurance for urban residents [OR=1.556, 95%CI (1.086, 2.230), P=0.016] and urban employees [OR=2.325, 95%CI (1.362, 3.967), P=0.002], having fewer children [OR=0.819, 95%CI (0.719, 0.933), P=0.003], and family history of stroke [OR=1.559, 95%CI (1.066, 2.282), P=0.022] were associated with greater adherence to antihypertensives; medical insurance for urban employees was associated with greater adherence to antidiabetics [OR=2.494, 95%CI (1.173, 5.300), P=0.018]. After adjusting for confounding factors, failure to regular use of antihypertensives [OR=2.617, 95%CI (1.414, 4.842), P=0.002], antidiabetics [OR=3.909, 95%CI (2.394, 6.380), P<0.001], and lipid-lowering agents [OR=4.828, 95%CI (2.581, 9.033), P<0.001] in patients with hypertension, diabetes, and dyslipidemia, respectively were associated with increased risk of ischemic stroke during the follow-up period. Regular use of lipid-lowering agents in patients with dyslipidemia was associated with an increased risk of intracerebral hemorrhage during the follow-up [OR=4.371, 95%CI (1.156, 16.530), P=0.030]. Conclusions The prevalences of hypertension, diabetes, and dyslipidemia are high in high-risk individuals of stroke in Sichuan province. However, the treatment rates are unsatisfactory, and the medication adherence is poor. The medication adherence is affected by a variety of demographic and socioeconomic factors. Regular treatments of hypertension, diabetes, and dyslipidemia reduce the risk of ischemic stroke in individuals at high risk of stroke, but regular use of lipid-lowering agents in patients with dyslipidemia is associated with an increased risk of intracerebral hemorrhage during the follow-up.