Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergic disorder with a well-characterised clinical phenotype, but limited understanding of factors associated with food cross-reactivity, severity and tolerance. Methods: A retrospective cohort study spanning 20 years on children with acute FPIES from a single paediatric tertiary centre in New South Wales, Australia focusing on identifying food trigger co-associations and factors associated with reaction severity, multiple trigger FPIES and/or tolerance was performed. Results: 169 individuals with 329 recorded FPIES episodes between 1997 and 2017 were included. 49% were male. The median age at first FPIES reaction was 5 months and median age at diagnosis was 9 months. 73% experienced at least one severe FPIES reaction. Rice (45%), cow’s milk (30%), soy (13%) were the most common triggers. FPIES to rice or cow’s milk were strongly associated with increased odds of having multiple trigger FPIES. Associations between causative foods were seen with rice/oats, cow’s milk/soy, and fish/shellfish. No factors were associated with increased risk of severe reactions. Infants with rice and grains FPIES outgrew their reactions at an earlier age, compared to those with fish FPIES. Conclusions: Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergic disorder with a well-characterised clinical phenotype, but limited understanding of factors associated with food cross-reactivity, severity and tolerance. Methods: A retrospective cohort study spanning 20 years on children with acute FPIES from a single paediatric tertiary centre in New South Wales, Australia focusing on identifying food trigger co-associations and factors associated with reaction severity, multiple trigger FPIES and/or tolerance was performed. Results: 169 individuals with 329 recorded FPIES episodes between 1997 and 2017 were included. 49% were male. The median age at first FPIES reaction was 5 months and median age at diagnosis was 9 months. 73% experienced at least one severe FPIES reaction. Rice (45%), cow’s milk (30%), soy (13%) were the most common triggers. FPIES to rice or cow’s milk were strongly associated with increased odds of having multiple trigger FPIES. The odds of having multiple food FPIES and severe reactions were slightly decreased with vaginal delivery. No factors were associated with increased risk of severe reactions. Infants with rice and grains FPIES outgrew their reactions at an earlier age, compared to those with fish FPIES. Conclusions: Rice remains the most common trigger for FPIES in this region with co-associations between rice/oats and cow’s milk/soy observed. The co-associations among food groups suggest that taxonomically related foods share similar protein structure and trigger similar mechanisms of antigen recognition. Vaginal delivery appears to have a mild protective effect on the development of multiple FPIES and severe reactions.