Early detection of zoonotic diseases allows for the implementation of early response measures, reducing loss of human life and economic disruption. We implemented a surveillance system in hospitals in Bangladesh to screen acutely ill hospitalized patients with severe respiratory infection and meningoencephalitis for zoonotic exposures. Patients were screened for the risk of zoonotic exposures with five questions covering vocational exposures, sick domestic animal and wild animal contact, and date palm sap consumption in the three weeks preceding illness onset. Patients giving at least one positive response were considered a potential zoonotic exposure. From September 2013 to March 2017, a total of 11 429 hospitalized patients across 14 participating hospitals were screened for exposures. Overall, 2% of patients reported a potential zoonotic exposure in the three-week period prior to becoming ill. Sixteen per cent of hospitalized patients with reported exposures died. After routine surveillance diagnostic testing, 88% of patients admitted to the hospital after a potential zoonotic exposure did not have a laboratory diagnosed aetiology for their illness. Hospital-based surveillance systems such as the Bangladeshi example presented here could play an important future role in the early detection of zoonotic spillover diseases. This article is part of the theme issue Dynamic and integrative approaches to understanding pathogen spillover.