(1) Background: we aimed to describe the disease-specific quality of life (QoL) of ischemic stroke patients treated with acute revascularization therapy, its evolution from 6 months to 12 months, and associated factors. (2) Methods: QoL was assessed with the SS-QoL in consecutive patients treated with either intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT). Variables associated with QoL scores and its evolution were studied using multivariate mixed models, and interaction with time. Analyses were performed in four domains of SS-QoL: self-care, mobility, mood, and social roles. (3) Results: Among the 501 included patients (mean (sd) age 68.9 (14.5), 49% women), lower post-stroke QoL was independently related to lower level of school education, prestroke mRS > 2, and 24 h NIHSS score > 4. Independent predictors of unfavorable evolution of QoL over time were age <75 years (Mobility p = 0.0194 and Mood p = 0.0015), NIHSS score ≤ 4, (Self-care p = 0.0053 and Mood p = 0.0048), and modified Rankin Scale score ≤ 2 (Social roles, p = 0.0006). Revascularization therapy had no significant effect on the QoL scores, but patients treated with MT (alone or as bridging therapy) had significantly greater improvement in mobility score between 6 and 12 months than patients treated with IVT alone (p = 0.0072). (4) Conclusion: QoL evolution over one year had only slight variation and was associated with the modalities of acute treatment, age, and stroke severity.