In this study, we aimed to assess the effects of early robot-assisted rehabilitation using the MOTOmed letto 2 on neurological recovery, disease severity, the rate and severity of multiple organ dysfunction syndrome, and the rate of venous thromboembolism in acute stroke patients in the intensive care unit (ICU), including patients requiring mechanical ventilation. This case-control study included 66 patients (49 men and 17 women; median age, 59 years) with acute ischemic stroke and cerebral hemorrhage admitted to the ICU. Patients were divided into two comparable groups, the intervention group (n = 33) and the control group (n = 33), and monitored from admission to day 21. After admission, both groups received standard rehabilitation, and patients in the intervention group also received robot-assisted arm and leg therapy. The groups had similar median Glasgow coma scale (GCS), National Institutes of Health Stroke Scale (NIHSS), APACHE II, and multiple organ dysfunction scale (MODS) scores on admission. There were no significant differences in neurological and medical outcomes on day 21 between the intervention and control groups (median GCS: 15 vs. 15, p = 0.32; median NIHSS 11 vs. 15, p > 0.05; median APACHE II: 6 vs. 9, p > 0.05; median MODS: 0 vs. 1, p > 0.05). The prevalence of multiple organ dysfunction syndrome and deep venous thrombosis (DVT) on day 21 was also similar in the intervention and control groups (60% vs. 67%, p > 0.05, and 58% vs. 45%, p > 0.05, respectively). However, the prevalence of severe multiple organ dysfunction syndrome, the incidence of pulmonary embolism, and the mortality rate were lower in the intervention group compared with the control group (14% vs. 41%, p < 0.05; 12% vs. 33%; p < 0.05; 12% vs. 39%, p < 0.05, respectively). Our results indicate that early robot-assisted therapy in patients with severe stroke admitted to the ICU reduces the rate of pulmonary embolism, the incidence of severe multiple organ dysfunction, and mortality on day 21, but does not influence neurological outcomes or the rate of deep vein thrombosis. © 2016, Pleiades Publishing, Inc.