Neonatal intensive care management (NICM) may be required for high risk or critically ill neonates for survival or stabilization. Apart from various life support systems, NICM involves the use of different classes of drugs, and the pattern of use mainly determined by the prevailing clinical conditions and complications, and the desired therapeutic objectives. As there are few systemic studies reported in the Indian literature, the present study was taken up. OBJECTIVES: To study the pattern of drug use in NICM, criteria for drug selection and dose individualization, to assess the efficacy and safety of medications and record drug interactions. METHODS: The pattern of drug use was assessed prospectively in 500 consecutive subjects admitted to NICU. The number of drugs used, therapeutic class, dose, route, frequency and duration of administration, the purpose of use, criteria for selection were recorded. The efficacy and safety of the medications was assessed by the treatment outcome and observing for any adverse events or drug interactions. RESULTS: Different therapeutic classes of drugs were used as per the prevailing clinical conditions or complications. The total number of drugs available for prescription from different class of drugs was 18, with an average of 3.6 per subject. Anti microbial agents (AMAs) were the most commonly used drugs, chosen empirically and used in combination for prophylaxis or control of infections. Other classes of drugs were used for specific indications. The treatment outcome was very good in most of the subjects and no drug related adverse events or interactions were observed. INTERPRETATION AND CONCLUSION: Most of the problems and complications in high risk and critically ill neonates can be prevented or controlled by judicious use of several classes of drugs, properly chosen and individualized to the given situation, without producing serious adverse events and interactions. Drugs play an important role in improving the outcome.