Objective To assess the clinical efficacy of ultrasonic atomization of penicillin combined with erythromycin in children with acute suppurative tonsillitis. Methods From July 2007 to December 2007, 70 children with a confirmed diagnosis of acute suppurative tonsillitis were randomized into two groups. Thirty-one patients in the control group received continuous 5-day treatment of routine intravenous drip of penicillin (200000units/ (kg?d)), twice a day, while 39patients in the trial group received, in addition to the routine treatment, another 5-day treatment of ultrasonic atomization of 0.1 g erythromycin and 10ml saline diluted by 10ml sterile water, 15min for each treatment, twice a day. Observation of the clinical efficacy of the two groups and statistical analyses were conducted. Results The cure rate and total effective rate of the trial group were 61.54% and 97.44%, and those of the control group were 35.48% and 77.42%, respectively. The pyretolysis rates at 48 h and 72 h in the trial group were 75.36% and 89.74%, and those in the control group were 45.16% and 61.29%, respectively. The improvement rates of pharyngodynia at 48 h and 72 h in the trial group were 76.92% and 92.31%, and those in the control group were 48.39% and 70.97%, respectively. The results of both rank sum test and chi-square test revealed significant differences between the trial group and the control groups (Plt;0.05), which indicated that the trial group was superior to the control group in terms of cure rate, total effectiveness rate, pyretolysis rate and improvement of pharyngodynia. During ultrasonic atomization, 3 patients experienced mild nausea and vomiting, all of which disappeared after rest. No other adverse reactions were recorded. Conclusions Ultrasonic atomization of penicillin combined with erythromycin for children with acute suppurative tonsillitis is worthy of clinical application due to its better efficacy and safety profile.