Background Adverse drug reactions (ADRs) constitute major clinical burden of public health concern. Intensive adverse drug reactions monitoring in hospitals, though advocated are rare. Aims Intensive monitoring of medical patients for ADRs to assess incidence, risk factors and fatality of ADRs leading to hospital admission or occurring in the hospital. Research design and methods Prospective cohort study on 1280 adult patients admitted to the six medical wards of a tertiary institution over a 12-month period. Patients were assessed for ADRs during and throughout admission. Causality assessment and preventability of ADRs were assessed. Results Sixty-seven (5.2%) patients had ADRs, which was the cause of admission in 46 (3.6%), and majority 61(91%) of the ADRs were preventable. NSAIDs, 14 (20.3%), antidiabetics, 12 (17.4%) and antibacterial, 11 (15.8%) were the most suspected drugs. Gastrointestinal tract (37%), CNS (30.2%), and skin (24.7%) were the most affected organ/systems, while upper GI bleeding and hypoglycaemia were the most observed ADRs. ADRs led to deaths in 7(10.4%) patients, with overall case fatality rate of 0.5%. Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis 3/7(42.9%) had the highest fatality rate. Risk factors, relative risk, 95% confidence interval for ADRs were alcohol intake, 1.7 (1.04, 2.80) and duration of hospital stay, 2.0 (1.16, 3.26). Conclusions Preventable ADRs are common and important cause of hospitalization and inpatients’ morbidity and mortality among medical patients in Nigeria. Upper GI bleeding and hypoglycaemia, resulting from NSAIDs and antidiabetic drugs were the most observed ADRs. Strategic planning for intensive follow up of ADRs in Nigeria is advocated.