Introduction: Neonatal opioid withdrawal syndrome occurs after exposure during pregnancies of mothers with an opioid use disorder. If non-pharmacological treatment is insufficient, pharmacological options are preferred, but a common treatment guideline has not yet been determined. Sublingual buprenorphine tablet is more prominent in the treatment. Since oral alternatives are not available in many clinics, as in our unit, parenteral morphine is still the drug of the first choice. In this paper, we reported that two babies with neonatal opioid withdrawal syndrome were successfully treated with a buprenorphine/naloxone combination, which was not previously shown in the literature. Cases: We followed two babies whose mothers had an opioid use disorder during their pregnancies. The modified Finnegan scoring scale was used for the assessment of the babies. Both infants developed persistent seizures with resistant withdrawal signs. An effective parenteral route could not be provided due to hemodynamic instability. Thus, IV morphine could not be used. Due to the lack of oral treatment alternatives, first, we tried phenobarbital up to 40 mg/kg orally. Afterward, we used buprenorphine/naloxone combined tablet sublingually, which has not been used in children before. Detailed written consent was obtained from the parents for the emergency use of this drug in advance. Shortly after this treatment, the seizures and withdrawal signs were controlled. There were no adverse effects and babies were discharged fully recovered. Conclusion: Sublingual Buprenorphine 2 mg + Naloxone 0.5 mg (4:1) tablet could be used efficiently and without side effects to treat neonatal opioid withdrawal syndrome.