Background: India is the third largest producer and exporter of medicines to most of the countries. The World Medicine Situation Report 2011 states that 65% persons in India do not have access to essential medicines. While, huge unethical prescribing ofdrugs for monetary gains has been a second major cause of rural indebtedness. Aims and Objectives: The primary objective of the study was to compare the Knowledge, Attitude and Practices of Essential Medicines among Medical Practitioners of a Medical College and Private Medical General Practitioners of an urban place, e.g. Perambalur District of South India. Materials and Methods: After ethical approval, the study was started, in Dhanalakshmi Srinivasan Medical College and Hospital (DSMCH), Siruvachur-621113, Perambalur, Tamil Nadu. It was a questionnaire based study. The faculties of the DSMCH and Medical Private Practitioner of Perambalur district included as participants in the study. We distributed knowledge, attitude and practice (KAP) based 15multiple choice questions on National Essential Medicine List, 2011 (NEML) to each healthcare professionals (HCPs) to attempt within 15 minutes. Results: Overall, Knowledge, attitude and practices regarding NEML 2011 were 57.06%, 38.36%; 51.16%, 51.82%; 21.73%, 28.7% to HCP from DSMCH and HCP from Perambalur district, respectively. Whereas, 42.2 % HCPs from DSMCH and 44.7 % HCPs from Perambalur district were prescribed branded and generic drugs both. Conclusion: The result’s data shows that regular awareness programmes should be conducted to update knowledge, change attitude and practices regarding essential medicines to serve the society as best as possible.