Objective To investigate the predictive factors of clinical progression and short-term prognosis of cerebral infarction caused by large artery atherosclerosis (LAA). MethodsPatients with acute LAA cerebral infarction who were hospitalized in the Department of Neurology, Lianyungang Hospital of Traditional Chinese Medicine between January 2016 and May 2019 were included. On admission, the patients’ medical history was collected. The degree of neurological deficit was assessed, blood pressure, blood glucose, blood lipids, plasma homocysteine, lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured, and intracranial and extracranial blood vessels related test results were collected. Within 72 hours of onset, the Scandinavian Stroke Scale (SSS) was used to determine whether the patients’ condition progressed. The modified Rankin scale was used to evaluate the short-term prognosis at 30 days of onset. The related factors of clinical progression and short-term prognosis of LAA cerebral infarction were analyzed. Results Finally, 100 patients were included. According to the SSS assessment results within 72 hours of onset, 27 cases were divided into the progression group and 73 cases in the non-progression group. There was no significant difference in gender and age between the two groups (P>0.05). According to the evaluation results of the modified Rankin scale at 30 days of onset, they were divided into 31 cases in the poor prognosis group and 69 cases in the good prognosis group. There was no significant difference in gender and age between the two groups (P>0.05). Logistic regression analysis showed that plasma Lp-PLA2 [odds ratio (OR)=1.013, 95% confidence interval (CI) (1.007, 1.018), P<0.001], SSS score [OR=0.910, 95%CI (0.842, 0.985), P=0.019], and history of hypertension [OR=5.527, 95%CI (1.241, 24.613), P=0.025] were the predictors of disease progression within 72 hours. SSS score [OR=0.849, 95%CI (0.744, 0.930), P<0.001], carotid artery stenosis [OR=9.536, 95%CI (1.395, 65.169), P=0.021] and progressive stroke [OR=8.873, 95%CI (1.937, 40.640), P=0.005] were the predictors of short-term prognosis of LAA cerebral infarction. Conclusions History of hypertension and high levels of plasma Lp-PLA2 are predictors of early progression of cerebral infarction. Carotid artery stenosis and progressive stroke are predictors of adverse outcomes in the acute phase of cerebral infarction. Neurological scores on admission was a predictor for short-term adverse outcomes in the early and acute phases.