Aim of study: Comparing the efficacy of combination (Midazolam – Hydroxyzine) with and without nitrous oxide and oxygen in sedating uncooperating school children undergoing dental treatment. Materials and Methods: This was a prospective, triple blind, randomized, cross over, clinical study of uncooperative school children in need of two sessions of Bilateral mandibular dental treatment. 30 children ages (6-9) years, were randomly selected to receive one of two regimens: Regimen (A) contain oral midazolam (M) 7.5 mg and hydroxyzine (H) 10 mg with oxygen (O2) 100%, while Regimen (B) contain oral midazolam (M) 7.5 mg and hydroxyzine (H) 10 mg with nitrous oxide\oxygen (N2O\O2) 50% . And in the second session, the other regimen was administered. the behavior was assessed using modified Houpt rating scale by reviewing the records of patients in pretreatment stage ( injection, rapper dam, operating dental drill without touching the tooth then with touching it) and during treatment stages ( drilling, restoration ). Beside recording the vital signs. Results: Comparing the overall assessment of the two regimens the success rate was (86.67%) in regimen (A) and (93.34%) in regimen (B). No significant statistical difference existed between the two regimes. The vital signs remained within normal limits in all cases and no series side effects appeared.