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Background: Few studies have compared the etiology and clinical features between pure lateral medullary infarction (LMI) and pure medial medullary infarction (MMI). Methods: All patients included were hospitalized at The First Affiliated Hospital and The Second Affiliated Hospital of Wenzhou Medical University from January 2015 to July 2020. Their risk factors, clinical manifestation, stroke mechanisms and short‐term prognosis were analyzed retrospectively. Results: Among the 387 patients enrolled, 266 (68.7%) had LMI, 109 (28.2%) had MMI, and 12 (3.1%) (nine men and three women) had LMI plus MMI. We analyzed the 375 patients of LMI and MMI. The average ages of LMI and MMI were 59.4 years and 62.69 years, respectively. Univariate analysis and multivariable logistic regression was used to investigate the existing risk factors of MMI relative to LMI. Prior infarction, poor glycemic control, and atherosclerosis were more frequently associated with MMI than with LMI. The clinical manifestation was significantly different between LMI and MMI. We used modified Rankin Scale (mRS) score as the short‐term prognostic evaluation criteria, and MMI appeared worse than LMI. Conclusions: This study reveals that: (1) patients with MMI are older than those with LMI; (2) prior infarction, poor glycemic control, and atherosclerosis are independent risk factors of MMI than that of LMI; (3) the clinical manifestations of LMI and MMI are heterogeneous; (4) short‐term prognosis of MMI is worse than LMI. [ABSTRACT FROM AUTHOR]