Background: Location-specific hematoma volume thresholds are associated with poor outcomes and can inform surgical trial inclusion criteria and clinical decision rules for hematoma evacuation. Methods: We performed a secondary analysis of the ATACH-2 and INTERACT2 clinical trials. We evaluated the associations between intraparenchymal location-specific hematoma volume cutoffs (basal ganglia, thalamus and lobar) and poor outcome (modified Rankin Scale 4-6). Using 24-hour CT scans, we calculated Youden’s index for each hematoma location to determine the optimal location-specific volume thresholds that predict outcomes. We calculated odds ratios (OR) of poor outcome through multivariable logistic regression models for each location. Results: Out of 1691 patients, 919, 551 and 221 were diagnosed with basal ganglia, thalamus and lobar intracerebral hemorrhage (ICH), respectively. Location-specific hematoma volume cutoffs most predictive of a poor outcome (mRS 4-6) were 22.24 mL for basal ganglia ICH (OR 4.82, 95% CI 3.19-7.27), 8.13 mL for thalamus ICH (OR 2.73, 95% CI 1.62-4.59) and 21.99 mL for lobar ICH (OR 6.31, 95% CI 2.53-15.74). Conclusions: Hematoma volumes associated with poor outcomes vary by location, supporting the idea that location-specific “hematoma volume tolerances” exist. Our results provide important data on location-specific hematoma volume tolerances to inform clinical trials in ICH management.