Certain probiotics may prevent the development of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CDAD), but their effectiveness depends on both strain and dose. There are few data on nutritional interventions to control AAD/CDAD in the spinal cord injury (SCI) population. The present study aimed to assess (1) the efficacy of consuming a commercially produced probiotic containing at least 6·5 × 10⁹ live Lactobacillus casei Shirota (LcS) in reducing the incidence of AAD/CDAD, and (2) whether undernutrition and proton pump inhibitors (PPI) are risk factors for AAD/CDAD. A total of 164 SCI patients (50·1 (sd 17·8) years) with a requirement for antibiotics (median 21 d, range 5-366) were randomly allocated to receive LcS (n 76) or no probiotic (n 82). LcS was given once daily for the duration of the antibiotic course and continued for 7 days thereafter. Nutritional risk was assessed by the Spinal Nutrition Screening Tool. The LcS group had a significantly lower incidence of AAD (17·1 v. 54·9%, P< 0·001). At baseline, 65% of patients were at undernutrition risk. Undernutrition (64·1 v. 33·3%, P< 0·01) and the use of PPI (38·4 v. 12·1 %, P= 0·022) were found to be associated with AAD. However, no significant difference was observed in nutrient intake between the groups. The multivariate logistic regression analysis identified poor appetite ( < 1/2 meals eaten) (OR 5·04, 95% CI 1·28, 19·84) and no probiotic (OR 8·46, 95% CI 3·22, 22·20) as the independent risk factors for AAD. The present study indicated that LcS could reduce the incidence of AAD in hospitalised SCI patients. A randomised, placebo-controlled study is needed to confirm this apparent therapeutic success in order to translate into improved clinical outcomes.