As a gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO) has been implicated in cardiovascular diseases. We aimed to investigate the relationship between the clinical outcomes and plasma TMAO concentrations in patients with acute intracerebral hemorrhage. From January 2019 to October 2019, we prospectively enrolled intracerebral hemorrhage patients diagnosed within 6h of symptoms onset. Plasma TMAO levels was measured for all patients within 24h after admission. The primary outcome was functional outcome at 3months. Patients were dichotomized as good (modified Rankin scale 0-3) and poor (modified Rankin scale 4-6). Secondary outcome included early neurological deterioration (END) and hematoma enlargement (HE). There were 307 patients (57.7% male) with a mean age of 66.8years included in the study. The median TMAO levels was 3.2μmol/L. END, HE, and 3-month poor outcome were detected in 59 (19.2%), 54 (17.6%), and 139 (45.3%) patients, respectively. After adjusting for potential confounders, the odds ratio for the highest quartile of TMAO compared with the lowest quartile was 3.65 (95% confidence interval, 1.43-9.30) for 3-month poor outcome. Furthermore, multiple-adjusted spline regression model showed a linear association between TMAO levels and poor outcome at 3months (P = 0.013 for linearity). Similar significant findings were observed when functional outcome was analyzed by continuous mRS score. No association was found between TMAO levels and END and HE. The present study demonstrated that increased TMAO levels were independently correlated with 3-month function outcome after intracerebral hemorrhage.