OBJECTIVES Compare the cost-effectiveness of two distinct therapies, Intravenous Immunoglobulin (IVIg) and Plasma Exchange (PE) in the treatment of Guillain-Barré Syndrome, concerning the public health care system. METHODS A cross-sectional, economical analysis was conducted, including patients treated for GBS in the period from June, 2003 through June, 2008 in a public university affiliated hospital in south Brazil. The cost-effectiveness of the use of IVIg and PE in such patients was studied through the cost minimization method, considering direct medical costs only (albumin, IvIG, supplies, professional, hotel and capital costs; 2008 prices). Data were collected by chart reviews. RESULTS The total treatment cost for PE in a single patient was US$6,058.85 (±1,701.78 SD), and the same expense for IVIg was US$18,344.57 (± 12,259.56 SD) (p = 0.035). Total inpatient cost was US$25,729.79 (± 18,714.54 SD) in the PE group, and US$34,768.16 (±27,766.01 SD) (p=0.530) in the IVIg group. The main clinical outcome was improvement in the 7-point disability grade scale. The median of that measure in patients admitted with a severity grade 3 treated either with PE and IVIg was the same. Secondary outcomes, such as in-hospital stay, ICU stay, and number of days on mechanical ventilation revealed no statistically significant difference between treatments. CONCLUSIONS As the mean expenses of both therapeutic options are compared, one clearly stands-out as less onerous. We concluded that, in a public university affiliated hospital, plasma exchange is more cost-effective than intravenous immunoglobulin.