OBJECTIVE Neonates are more susceptible to drug interactions and adverse effects, and special care should be taken when prescribing medication to them. This study aimed to investigate drug usage in the neonatal intensive care unit of a tertiary care hospital. METHODS This prospective observational study was conducted on 98 patients at the Apollo tertiary care hospital (Bannerghatta, Bangalore, India) in a period of 6 months. The most common indications for neonatal intensive care unit admission, average number of drugs per patient, the most frequently used medication, distribution of patients based on the birth procedure, and possible drug interactions were collected from patient profiles. RESULTS Among the patients, 52% were males and 48% were females. Notably, 38% of patients were preterm, 60% were term, and only 2% were post-term. Also, 80.6% were born by cesarean section and 19.4% were born by normal vaginal delivery. The highest mean of drug use was in the patient of 1,000-1,500 g (8.06 per patient). Preterm was the most frequent indication for admission in neonatal intensive care unit, followed by hyperbilirubinemia and then respiratory distress syndrome. The most frequently used medication was vitamin K (99%) and antibiotics followed by dextrose. In different types of antibiotics, amikacin (41%), cefoperazone+sulbactam (35%), cephalosporin (1%), ceftriaxone (0.7%), and amoxicillin (0.3%) were commonly administered. There were some possible interactions, such as aminoglycoside with furosemide and calcium gluconate. CONCLUSIONS Premature birth and resulting low birth weight were the main reasons for drug prescription. High administration of antibiotics is probably an area of concern and should be seriously considered.