Objective To explore the 2 year cognitive trajectory of patients with acute caudate head infarction and the impact of infarct volume on cognitive impairment. Methods We consecutively enrolled patients with acute caudate head infarction admitted to Xi’an Central Hospital between January 2014 and January 2022. Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) at 1 week, 6-months, 12-months, 18-months and 24-months after admission. Infarct volume was measured via diffusion-weighted imaging. Spearman rank correlation was used to analyze the correlation between infarct volume and cognitive score changes; Friedman test with Bonferroni correction was applied for cross-time-point score comparison. Results A total of 25 patients completed the 24-months follow-up. The average was (62.08±8.90) years, the average infarct volume was (1 165.05±850.07) mm3. The average MoCA scores at the 5 time points were 20.40±4.46, 24.64±5.34, 24.48±5.65, 24.04±6.01 and 23.20±6.58. The average MMSE scores were 23.68±4.14, 26.92±4.33, 26.88±4.82, 26.76±4.85 and 26.32±5.04. The cognitive trajectory showed an initial rise followed by a decline within 24 months. MoCA score changes were strongly correlated with infarct volume (no significant correlation for MMSE). The difference in MoCA scores over the first 6 months was negatively correlated with infarct volume (P<0.001). 24-months MoCA changes were mainly attributed to visuospatial/executive function, language and delayed recall subdomains. Conclusion Caudate head infarct volume is associated with early-onset post-stroke cognitive impairment, with cognitive changes mainly driven by alterations in visuospatial/executive, language and delayed recall subdomains.