BACKGROUND: No epidemiological study has determined the association between the anion gap (AG) and all-cause mortality in cerebral infarction patients after treatment with rtPA. This study is aimed at using AG levels as a prognostic factor for evaluating cerebral infarction patients after receiving rtPA treatment and to help the resident physicians accurately evaluate the therapeutic plan of rtPA. METHODS: We extracted clinical data from the public database (MIMIC-IV database V1.0) and used the Kaplan-Meier curve to estimate the survival probabilities of cerebral infarction patients after rtPA treatment for the one-year, four-year, and whole period by log-rank test in 948 intensive care unit patients. Cox proportional hazard models were used to assess the association between AG and one-year, four-year, and whole period mortality in cerebral infarction patients after treatment with rtPA. RESULTS: Kaplan-Meier survival curve indicated a higher AG value is significantly associated with an increased risk of one-year, four-year, and whole-period all-cause mortality in cerebral infarction patients after treatment with rtPA. Model I adjusted for ethnicity, age, gender, and skin tone. Model II adjusted for ethnicity, age, gender, skin tone, hypertension, diabetes, coronary atherosclerosis, congestive heart failure, peripheral vascular, hyperlipidemia, acute myocardial infarction (AMI), respiratory failure, and end-stage renal diseaseesrd (ESRD). On the basis of model II, model III adjusted for WBC, BUN, creatinine, platelet, MCH, MCHC, MCV, RBC, and RDW. In addition, there was better predictive ability between higher AG levels and mortality in certain subgroups, such as patients with platelet ≤ 247, RBC > 3.11. CONCLUSION: Serum AG is positively related to all-cause mortality in cerebral infarction patients after treatment with rtPA.