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Background: Gender-related differences in stroke are issues of increasing interest. Post- stroke fatigue (PSF) is a frequently reported symptom affecting stroke survivors and is a predictor for death and increased disability.Aims: To evaluate gender differences and predictors in PSF in an urban predominantly minority cohort.Methods: Two-center, IRB approved, prospective study serving primarily African/Caribbean Americans. Eligible patients included ischemic stroke within 3 years. Aphasia, dementia or pre-existing depression were exclusions. PSF was assessed by Fatigue Assessment Score (FAS); depression by the Beck Depression Inventory (BDI). Primary outcome was FAS log-transformed due to its skewed distribution. Multiple linear regression determined gender differences in PSF, adjusted for prior stroke, diabetes (DM), atrial fibrillation (AF), hypertension (HTN) and the following dichotomized predictors: stroke severity (NIHSS >2), BDI score (≥11), age (≥55), and time from stroke onset (>30 days). First-order interactions between gender and other predictors were investigated. Chi square test was used to test for gender differences in the distribution of the other categorical predictors. P<0.05 was considered significant.Results: 150 patients, mean age 66 years (SD=13, range 30-93); 82 (55%) women. Higher rates of prior stroke (44% vs 28%, p=0.04) and AF (15% vs 4%, p=0.04) were present in women than in men. No gender differences were observed for the other predictors. We found that female gender was associated with 18% (95% CI: 4%-33%, p=0.009) higher levels of PSF, adjusted for other predictors. Two other predictors were associated with greater PSF severity: BDI ≥11 with 34% (95% CI: 14%-57%, p=0.0005) and NIHSS>2 with 14% (95% CI: 0.3%-29%, p=0.045) increase in the PSF. However, HTN was associated with 24% (95% CI: 9%-37%, p=0.004) decreased PSF severity. The 8 included predictors explained 30% of the variability in the PSF severity.Conclusions: In our urban, predominately minority cohort, women had more severe PSF than men. As the basis for PSF remains to be elucidated, our data suggest that gender-specific factors may modulate the magnitude of PSF. The protective effect of HTN on PSF severity is unclear and deserves further study.