To evaluate the effectiveness and relationship of prophylactic antibiotics (PA) with the results of tonsillectomy surgery. The study was conducted on 78 patients undergoing tonsillectomy. Among them is divided into 2 groups; Group A is the group using PA, including 39 patients studied prospectively and with longitudinal observation; Group B is the group using the previously used routine antibiotic treatment, including 39 patients retrospectively studied on medical records and medical examination records at follow-up visits. There are no conflicts of interest of research subjects in group A and group B. The number of cases using PA and routine antibiotic treatment was equal. The overall average age of the study subjects was 28.77 ± 9.13 years old, and the ratio of female/male was 1.05/1. After surgery, the pain level gradually decreased over time, and the change was statistically significant (p < 0.05). The average postoperative about pain level, secondary bleeding, progression of the tonsil cavity, infection, and recovery level between group A and group B was not statistically significant (p > 0.05). The effectiveness of using PA is equivalent to using routine antibiotics in post-tonsillectomy treatment, compared through indicators of post-operative pain, bleeding, progression of the tonsil cavity, bad breath, duration of vomiting, ear pain, return to eating solid foods, and postoperative time in the hospital.