BACKGROUND Severe Guillain-Barré syndrome (GBS) is associated with significant morbidity and also mortality. Identification of modifiable risk factors may help in reducing the morbidity and mortality. OBJECTIVE To study the prognostic factors in a selected cohort of mechanically ventilated GBS patients. METHODS Case records of GBS patients requiring mechanical ventilation admitted between 1997 and 2007 were analyzed. All patients satisfied the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for GBS. Primary outcome parameters included mortality and GBS disability (Hughes) scale score at discharge. RESULTS During the study period, 173 (118 men and 55 women; mean age of 33.5 ± 21 years) GBS patients were mechanically ventilated. A history of antecedent events was present in 83 (48%) patients. In addition to motor weakness, In all facial palsy was present in 106 (61%), bulbar palsy in 91 (53%), sensory involvement in 74 (43%), and symptomatic autonomic dysfunction in 27 (16%). The overall mortality was 10.4%. On univariate analysis the risk factors for mortality included elderly age (P = 0.014), autonomic dysfunction (P = 0.002), pulmonary complications (P = 0.011), hypokalemia (P = 0.011), and bleeding (P = 0.026). All these factors were significant in multivariate analysis except for bleeding from any site and hypokalemia. In univariate analysis factors associated with Hughes scale score ≤ 3 at discharge included younger age (P = 0.02), presence of bulbar symptoms (P = 0.03) and less severe weakness at admission (P = 0.02), slower evolution of disease over more than 3 days (P = 0.01), electrodiagnostic evidence of demyelinating neuropathy (P = 0.00), and absence of sepsis (P = 0.01), hyperkalemia (P = 0.0001), and anemia (P = 0.02). In multivariate analysis age was the only significant factor. CONCLUSIONS Early identification of modifiable risk factors, such as pulmonary involvement, autonomic dysfunction, hypokalemia, sepsis, bleeding, and nutritional complications, may reduce the mortality and morbidity associated with GBS.