We aimed to assess the occurrence and characteristics of antibiotic-associated adverse drug reactions (ADRs) in Malawi. Methods: We retrospectively reviewed 304 patient records from medical wards in three hospitals in Southern Malawi. A global trigger tool was applied for the detection of suspected ADRs, and we used the Naranjo scale, the World Health Organization classification and the Schumock and Thornton scale for causality, seriousness and preventability assessment respectively. ADRs were also further characterized according to anatomical systems. Statistical analysis was done in STATA 14.1. The Chi-square test was used to determine the association between categorical variables and logistic regression analysis was used to measure the strength of the association between various independent variables and the occurrence of ADRs. Results: Suspected ADRs were detected in 24% (73/304) of patients, of which 1.4% were definite, 15.1% were probable and 83.6% were possible ADRs. Most of the sADRs were gastrointestinal events (42.5%), followed by: musculoskeletal (26.3%); cardiovascular (16.3%); central nervous system (13.8%; and urinary events (1.3%). About 27% of the sADRs were serious events such as convulsions. The geriatric age group (≥65 years) was more likely to experience sADRs as compared to the younger age group, with an adjusted odds ratio (aOR) of 4.53, 95% CI (2.21-9.28), P<0.001. Patients taking more than one antibiotic medicine had a higher risk of developing sADRs as compared to patients who were administered one type of antibiotic medicine, aOR 2.14, 95% CI (1.18-3.90), p < 0.012. A long hospital stay of >3days was associated with a higher risk of sADRs with aOR of 5.11, 95% CI (2.47-10.55), p < 0.001 than those who stayed ≤ 3 days in the hospital. Conclusion: We found a higher prevalence of serious sADRs associated with antibiotic medicines than reported elsewhere. This may, among others, contribute to high patient mortality, poor treatment adherence, antibiotic resistance and increased cost of care.