Background: Prescription auditing is one of the important tool to avoid misuse of drugs and improves rational use of drugs. The performance of the health care providers related to the appropriate use of drugs can be accessed by analyzing the different prescribing indicators. An adverse drug reaction (ADR) can be defined as ‘an appreciably harmful or unpleasant reaction resulting from an intervention related to the use of a medicinal product. This can be assessed by using probability scale, severity assessment scales, etc. Objectives: The main objective of the study was to audit the prescriptions, evaluate the incidence of ADR and assess health related quality of life. Methodology: A Prospective interventional study was conducted in a tertiary care teaching hospital in south Kerala during the study period of 6 months. A total no.of 235 inpatients in general medicine department were included during the study. Results: Out of 235 prescriptions, 1742 drugs were analyzed using prescription auditing checklist. The average no.of drugs were prescribed about 7.41. The incidence of ADRs is 0.025 and 6 were identified and analyzed using Naranjo scale and Hartwig severity assessment scale. In health related quality of life shows significance in age, BMI, gender, socioeconomic status and prescribing indicators in different aspects. Conclusion: There is a need for improvement in the standards of prescription patterns in all aspects. The health related quality of life will helps to assess physical and mental attitudes of patients which may affect their drug therapy.