Abstract Background Diarrhea in foals can be associated with disruption of the intestinal microbiota (dysbiosis). Effective management of intestinal dysbiosis in foals has not been demonstrated. Hypothesis/Objectives Fecal microbiota transplantation (FMT) in foals with diarrhea influences the intestinal microbiota and improves clinical and clinicopathological outcomes. Animals Twenty-five foals <6 months of age with diarrhea and systemic inflammatory response syndrome at 3 veterinary hospitals. Methods A prospective randomized placebo-controlled cohort study. Foals in the FMT group (n = 19) or control group (n = 9) received FMT or electrolyte solution once daily for 3 days. Fecal samples were obtained on Day 0 (D0), D1, D2, D3, and D7. Within group and between group data analyses were performed for clinical, clinicopathological, and microbiota variables. Results Treatment had no effect on survival (FMT 79%; control 100%, P = .3) or resolution of diarrhea (FMT 68%; control 55%, P = .4). On D3, the white blood cell count of the FMT group was lower than the control group (D3 FMT group median 6.4 g/L [5-8.3 g/L]; D3 control group median 14.3 g/L [6.7-18.9 g/L] P = .04). Heart rate reduced over time in the FMT group (D0 median 80 bpm [60-150 bpm]; D2 median 70 bpm [52-110 bpm] [P = .005]; and D3 median 64, [54-102 bpm] [P < .001]). Phylum Verrucomicrobiota, genus Akkermansia, and family Prevotellaceae were enriched in the FMT group on D1 (linear discriminate analysis > 4). Conclusions and Clinical Importance In foals with diarrhea, FMT appears safe and can be associated with some clinical and microbiota changes suggestive of beneficial effect.