Background Although guidelines for secondary ischemic stroke have been developed, there is a gap between guidelines and clinic practice. Aims This study will investigate the current status of secondary ischemic stroke prevention in China, and implement a standard medical program in ischemic stroke and/or transient ischemic attack patients, and to examine the feasibility and efficacy of the program. Design This is a multicentre, parallel, randomized, open label, controlled trial to evaluate the feasibility and efficacy of a recommended guideline based program (SMART) in secondary stroke prevention. Forty-eight sites across Mainland China will participate in the trial. The number of enrolled patients in the study will be 4074. Primary outcome includes the proportion of patients adherent to eligible measures recommend by the SMART program, which is derived from current prevention guidelines for ischemic stroke, and the proportion of the patients achieving the treatment target. Secondary outcomes include new onset ischemic stroke, hemorrhagic stroke, acute coronary syndrome and all causes of death. The study has been registered on Clinicaltrials. gov (NCT00664846); to date, 3380 patients have been enrolled.