BACKGROUND & AIMS: To examine the effect of supplementation with probiotics on respiratory and gastrointestinal illness in healthy active men and women. METHODS: A randomised double-blind placebo-controlled trial was conducted. Four hundred and sixty five participants (241 males; age 35ౠ12๠(meanౠSD) and 224 females; age 36ౠ12๩ were assigned to one of three groups: Group 1 - Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) 2.0נ10(9)colony forming units per day, CFU per day, Group 2 - Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bi-07 (NCFM & Bi-07) 5נ10(9)ÆU each per day) or Group 3 - placebo mixed in a drink. RESULTS: The risk of an upper respiratory illness episode was significantly lower in the Bl-04 group (hazard ratio 0.73; 95% confidence interval 0.55-0.95; Pའ0.022) compared to placebo. There was no significant difference in illness risk between the NCFM & Bi-07 group (hazard ratio 0.81; 0.62-1.08; Pའ0.15) and the placebo group. There was a 0.7 and 0.9 month delay in the median time to an illness episode in the Bl-04 and NCFM & Bi-07 groups respectively compared to placebo (placebo 2.5 months; Bl-04 3.2 months; NCFM & Bi-07 3.4 months). There were insufficient GI illness episodes for analysis. The NCFM & Bi-07 group but not the Bl-04 group undertook significantly more physical activity (8.5%; 6.7%-10%; P༠0.003) than the placebo group. CONCLUSION: The probiotic Bl-04 appears to be a useful nutritional supplement in reducing the risk of URTI in healthy physically-active adults. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: Number ACTRN12611000130965.