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Gentamicin is one of the most frequently used antibiotics in neonatal units and there are many regimes in use based on weight and/or gestational age (GA). Direct costs include prescription and therapeutic drug monitoring (TDM). A retrospective audit (loop 1) identified 48 per cent trough and 51 per cent peak levels outside the desirable range (trough: ≤2; peak: 5‐10 mg/L). A prospective re‐audit (loop 2) showed improved results (15 per cent and 29 per cent), which improved further (11 per cent and 26 per cent) in loop 3. For loops 1, 2, and 3 the mean (±SD) trough levels were 2.16 (±1.04), 1.30 (± 0.63) and 1.23 (±0.62) respectively and peak levels were 5.05 (±1.87), 6.64 (±2.48), and 6.2 (±1.81) respectively. Cost savings occurred as the number of doses required was reduced by one‐third to 50 per cent, depending upon the infant characteristics. Furthermore, in 27 per cent of cases, gentamicin was discontinued before TDM was necessary. By completing the audit cycle improved quality of therapeutic care has been achieved, with more accurate drug monitoring targets achieved and reduced drug costs.