Paediatric antibiotic prescription is a major concern in terms of public health, since infections are the most frequent cause of childhood disease. The aim of this a hospital-based cross sectional study was to assess the pattern of antibiotic use in the Paediatric ward of Hawassa University referral hospital, southern-Ethiopia. Data was entered into a computer and statistical analysis was done using SPSS for windows version16. From the result of the study, the frequency and percentage of antibiotic prescriptions identified was 1381 (74.7%); (Wald test, p < 0.01), and the frequency and percentage of Injectable prescription was 1729 (93.6%); (Wald test, p < 0.01). The mean number of drugs prescribed per-prescription was 1.58±0.743. The mean of antibiotics prescriptions in preschool children was relatively higher (1.26; 95% C.I b/n 1.03-1.29) compared to other pediatric age groups. The use of antibiotic by pediatric age category was found to be significant (Pearson Chi-Square P= 0.037). Very strong positive correlation of antibiotic use was observed with generics prescriptions and injection prescriptions (0.740 and 0.731 with p-value < 0.01) respectively. The potential Drug-Drug Interactions (DDIs) identified in the study area was 66% (Fisher's Exact Test, P< 0.01). The availability of a set of key antimicrobial drugs in the hospital stores on the day of the study was 90.1%. The most frequently prescribed single antibiotic was penicillin G crystalline 146 (28.4%), While the most commonly prescribed multiple antibiotic prescriptions was ‘Ampicillin inj plus Gentamicin inj’ 113 (27%) followed by ‘Chloramphenicol inj plus Cloxacillin inj’ 60 (14.4%). From the result we can conclude that, there was a significant oral and injectable antibiotic utilization in the study area compared to similar studies conducted in other part of the world.