Objectives Plasma total homocysteine (tHcy) is a risk factor for ischemic stroke (IS) but its relationship with IS outcome is uncertain. Moreover, previous studies underrepresented older IS patients, although risk of both hyperhomocysteinemia and IS increases with age. We investigated whether, in elderly patients with acute IS, tHcy measured on admission to the Stroke Unit (SU) is an independent predictor of SU discharge outcomes. Materials and Methods Data are for 644 consecutive patients aged 80.3 ± 8.7 years, admitted to an Italian SU with diagnosis of acute IS. Plasma tHcy was measured on SU admission. Investigated outcomes included mortality during SU stay and poor functional status (modified Rankin Scale score ≥3) at SU discharge for survivors. The association of plasma tHcy with the study outcomes was assessed using Odds Ratios (OR) and their corresponding 95% confidence intervals (95%CI) from logistic regression models adjusted for demographics, pre‐stroke features, IS severity, and laboratory data on SU admission (serum C‐reactive protein, serum albumin, and renal function). Results Median plasma tHcy was 16.7 μmol/L (interquartile range, 13.0–23.3 μmol/L). Outcome incidence was 5.3% for mortality and 49.7% for poor functional status. Plasma tHcy was unrelated to mortality in both univariate and multivariable‐adjusted analyses. Conversely, plasma tHcy was associated with poor functional status of survivors in univariate analyses (P = 0.014). Multivariable‐adjusted analyses showed that, compared to normal homocysteinemia (tHcy <16 μmol/L), risk of being discharged with poor functional status significantly increased for moderate (tHcy ≥30 mol/L) but not mild (16.0–29.9 μmol/L) hyperhomocysteinemia. Conclusions In elderly patients with acute IS, high admission plasma tHcy is unrelated to mortality during SU stay but is an independent predictor of poor functional status at SU discharge in survivors. The association, however, is limited to patients with moderate hyperhomocysteinemia. Blood total homocysteine (tHcy) is an acknowledged risk factor for ischemic stroke (IS), but it is still uncertain whether homocisteinemia is associated with outcome of acute IS. This study shows that, in elderly patients with acute IS admitted to Stroke Unit (SU), high admission plasma tHcy is unrelated to mortality during SU stay, but is an independent predictor of poor functional status at SU discharge in survivors. The association, however, is limited to patients with moderate hyperhomocysteinemia.