Introduction: Small vessel disease (SVD) causes most spontaneous intracerebral haemorrhage (ICH) and is associated with widespread microstructural brain tissue disruption, which can be quantified via diffusion tensor imaging (DTI) metrics: mean diffusivity (MD) and fractional anisotropy (FA). Little is known about the impact of whole-brain microstructural alterations after SVD-related ICH. We aimed to investigate: (1) association between whole-brain DTI metrics and functional outcome after ICH; and (2) predictive ability of these metrics compared to the pre-existing ICH score. Methods: Sixty-eight patients (38.2% lobar) were retrospectively included. We assessed whole-brain DTI metrics (obtained within 5 days after ICH) in cortical and deep grey matter and white matter. We used univariable logistic regression to assess the associations between DTI and clinical-radiological variables and poor outcome (modified Rankin Scale > 2). We determined the optimal predictive variables (via LASSO estimation) in: model 1 (DTI variables only), model 2 (DTI plus non-DTI variables), model 3 (DTI plus ICH score). Optimism-adjusted C-statistics were calculated for each model and compared (likelihood ratio test) against the ICH score. Results: Deep grey matter MD (OR 1.04 [95% CI 1.01–1.07], p = 0.010) and white matter MD (OR 1.11 [95% CI 1.01–1.23], p = 0.044) were associated (univariate analysis) with poor outcome. Discrimination values for model 1 (0.67 [95% CI 0.52–0.83]), model 2 (0.71 [95% CI 0.57–0.85) and model 3 (0.66 [95% CI 0.52–0.82]) were all significantly higher than the ICH score (0.62 [95% CI 0.49–0.75]). Conclusion: Our exploratory study suggests that whole-brain microstructural disruption measured by DTI is associated with poor 6-month functional outcome after SVD-related ICH. Whole-brain DTI metrics performed better at predicting recovery than the existing ICH score
