OBJECTIVES: To evaluate Phramongkutklao CPG for treatment of neonatal infection in newborn infants with maternal history of PROM for ≥18 hours and the impact on saving hospital cost. METHODS: Prospective cohort study. Infants with maternal history of PROM were categorized into 1 of 3 groups: group I, having symptoms within 6 hours after birth; group II, having history of maternal chorioamnionitis and group III, healthy infants without history of maternal chorioamnionitis. All infants in group I and II were treated with antibiotics. Infants in group III were ranked by using PROM scoring system. The success of CPG was defined as no re-admission due to infection occurred within 28 days of age. Logistic regression was used to determine the association between neonatal infection and risk factors. RESULTS: In total, 109 of 5,182 (2.10%) infants born during study period had maternal history of PROM, 5 cases were excluded. Twenty-nine of 104 (27.88%) infants had infection and were treated with antibiotics. The CPG successfully identified different risk of infection in 102 of 104 (98.08%) infants. The use of CPG reduced a number of infants treated with antibiotics from 81 to 38 (53.09%) compared to the previous strategies. The relative risk of 1-minute Apgar scores ≤ 5, duration of PROM > 72 hours, gestational age < 34 wk, birth weight 1500-2500g and birth weight < 1500g were 3.82 (95%CI 2.43-5.99), 3.47 (95%CI 1.56-7.72), 5.33 (95%CI 2.77-10.25), 3.40 (95%CI 1.84-6.28) and 6.17 (95%CI 3.67-10.35), respectively. Logistic regression analysis equation was log [Infection Rate] = 4.148 - 3.028 [gestational age <34 wk] -2.444 [gestation age 34-37 wk] - 3.029 [1-minute Apgar score] (R2= 0.84). Using CPG reduced expenditure for treatment from 469,395 Baht to 237,700 Baht or 139,017 Baht per year. CONCLUSIONS: Phramongkutklao CPG on PROM is safe and cost saving for managing newborn infants at risk.