Background and Study Aims: The need for gastrointestinal procedures, such as upper gastrointestinal endoscopies (UGIE), in children has been increased in the recent years. Our study sought to compare the safety, the efficacy, the ease of intravenous (IV) line placement and the ease of the parents' separation of the synergistic sedation with an oral dose of midazolam as premedication combined with IV propofol versus IV propofol alone in diagnostic UGIE in children. To the best of our knowledge, this is the only prospective, randomized study in this issue. Material and Methods: 54 consecutive children (age over 3 yr) who underwent UGIE were randomly assigned to one of the two medication regimens. Patients in group A (n=26, mean age: 8.1 yr) received orally midazolam (0.5 mg/kgr). 30 minutes after the midazolam dose given, repeated IV doses of propofol 0.5 mg/kgr were administered titrated to achieve the level of deep sedation. Patients in group B (n=28, mean age: 9 yr) received IV propofol alone with the same methodology and sedation end point. The ease of IV line placement and the ease of the parents' separation were assessed by a three and five point scale, respectively. The patient's comfort level was assessed by a three point scale. The time to recover from the sedation was assessed by using the REACT score. Results: The mean dose (1.8±0.7 mg/kg) of propofol administered in group A patients was remarkably lower compared to that (2.9±0.9 mg/kg) of group B. Multivariate stepwise logistic regression analysis revealed that among sex, age, ASA grade and the sort of sedation, the synergistic sedation was the only factor associated with the ease of IV line placement (chi-square=16.3, p<0.001) and the ease of parents' separation (chi-square=41.6, p<0.001). Additional multivariate stepwise logistic regression analysis revealed that among sex, age, ASA grade and the sort of sedation, the synergistic sedation was the only factor associated with a higher level of patient comfort (chi-square=35.5, p<0.001). The recovery time was significantly shorter in group B patients (7.7±3.6 min) compared to that of group A (25.9±4.1 min) (p<0.01). The two regimens were equally safe. Conclusions: Our data suggest that the synergistic sedation with oral midazolame as a premedication and IV propofol was superior to sedation with IV propofol alone as far as the IV line placement, the parents' separation and patient comfort in UGIE in children. Background and Study Aims: The need for gastrointestinal procedures, such as upper gastrointestinal endoscopies (UGIE), in children has been increased in the recent years. Our study sought to compare the safety, the efficacy, the ease of intravenous (IV) line placement and the ease of the parents' separation of the synergistic sedation with an oral dose of midazolam as premedication combined with IV propofol versus IV propofol alone in diagnostic UGIE in children. To the best of our knowledge, this is the only prospective, randomized study in this issue. Material and Methods: 54 consecutive children (age over 3 yr) who underwent UGIE were randomly assigned to one of the two medication regimens. Patients in group A (n=26, mean age: 8.1 yr) received orally midazolam (0.5 mg/kgr). 30 minutes after the midazolam dose given, repeated IV doses of propofol 0.5 mg/kgr were administered titrated to achieve the level of deep sedation. Patients in group B (n=28, mean age: 9 yr) received IV propofol alone with the same methodology and sedation end point. The ease of IV line placement and the ease of the parents' separation were assessed by a three and five point scale, respectively. The patient's comfort level was assessed by a three point scale. The time to recover from the sedation was assessed by using the REACT score. Results: The mean dose (1.8±0.7 mg/kg) of propofol administered in group A patients was remarkably lower compared to that (2.9±0.9 mg/kg) of group B. Multivariate stepwise logistic regression analysis revealed that among sex, age, ASA grade and the sort of sedation, the synergistic sedation was the only factor associated with the ease of IV line placement (chi-square=16.3, p<0.001) and the ease of parents' separation (chi-square=41.6, p<0.001). Additional multivariate stepwise logistic regression analysis revealed that among sex, age, ASA grade and the sort of sedation, the synergistic sedation was the only factor associated with a higher level of patient comfort (chi-square=35.5, p<0.001). The recovery time was significantly shorter in group B patients (7.7±3.6 min) compared to that of group A (25.9±4.1 min) (p<0.01). The two regimens were equally safe. Conclusions: Our data suggest that the synergistic sedation with oral midazolame as a premedication and IV propofol was superior to sedation with IV propofol alone as far as the IV line placement, the parents' separation and patient comfort in UGIE in children.