BACKGROUND AND AIMS: The most common symptoms of Covid-19 are respiratory; however, gastrointestinal symptoms are present in up to 50% of patients. We aimed to determine characteristics associated with the development of gastrointestinal symptoms in patients with Covid-19. METHODS: A case-control study of adults hospitalized for Covid-19 was conducted across a geographically diverse alliance of 36 US and Canadian medical centers. Data were manually abstracted from electronic health records and analyzed using regression analyses to determine characteristics associated with any gastrointestinal symptoms and diarrhea specifically. RESULTS: Of 1406 patients, 540 (38%) reported at least one gastrointestinal symptom and 346 (25%) reported diarrhea. Older patients (≥ 80 years) had significantly lower rates of any gastrointestinal symptoms and diarrhea (vs. patients 18-79 years, OR 0.41, p < 0.01 and OR 0.43 p = 0.01, respectively), while those with IBS (OR 7.70, p = 0.02 and OR 6.72, p < 0.01, respectively) and on immunosuppressive therapy (OR = 1.56, p = 0.02) had higher rates of any gastrointestinal symptom and diarrhea. Patients with constitutional symptoms exhibited significantly higher rates (OR 1.91, p < 0.01), while those with pulmonary disease alone had lower rates of gastrointestinal symptoms (OR 0.23, p = 0.01). A significant interaction between constitutional symptoms and pre-existing pulmonary conditions was observed. CONCLUSIONS: Several patient- and disease-specific characteristics associate with gastrointestinal symptoms in patients with Covid-19. Knowledge of these may provide insights into associated pathophysiologic mechanisms, and help health care professionals provide targeted attention to reduce morbidity related to Covid-19.