Ventilator-associated pneumonia (VAP) occurs in more than half of mechanically ventilated patients with Guillain-Barr, syndrome (GBS) and is associated with prolonged mechanical ventilation (MV). We investigated the impact of selective decontamination of the digestive tract (SDD), an intervention that reduces hospital acquired infections in ICU patients, on duration of MV in GBS and neurological outcome at 6 months. We performed a retrospective study in mechanically ventilated GBS patients in the Netherlands. We compared patients treated with and without SDD. Main outcomes were duration of MV and the ability to walk independently at 6 months. Statistical comparison was done with logistic and ordinal regression analyses. We included 124 GBS patients on MV at 2 weeks after first symptoms (SDD, n = 54 and non-SDD, n = 70). The median duration of MV without SDD was 42 days (interquartile range, IQR 25-77 days) versus 29 days with SDD (IQR 17-45 days). Median duration of MV for all included patients was 35 days. The adjusted odds ratio (OR) for duration of MV > 35 days in the SDD versus the non-SDD cohort was 0.37 (95% CI 0.17-0.77). SDD did not affect neurological recovery after 6 months from first symptoms. VAP occurred in 12% (95% CI 2-22%) in the SDD cohort and in 47% (95% CI 35-59%) in the non-SDD cohort. SDD in mechanically ventilated GBS patients reduced the time on the ventilator, probably by preventing VAP, but did not affect neurological recovery after 6 months.