The study evaluated the effect of intra-alveolar administration of a thermosetting gel containing doxycyclyne hylcate 3% on patient discomfort after third molar surgery. Eighty-five consecutive patients requiring surgical removal of a single maxillary or mandibular impacted third molar were randomly selected and divided into 2 groups. After the onset of local anaesthesia, the experimental groups received 2 different antibiotic protocols: rifampicin for the first group and a thermosetting gel containing doxycyclyne hylcate 3% for the second group. Standardized surgical protocols were followed. The patients' perception of the severity of symptoms (pain, swelling, reddening, bleeding and body temperature) was assessed with a follow-up questionnaire (PoSSe scale). On the second postoperative day, pain, reddening and bleeding showed a statistically significant reduction in Group 2 compared with Group 1. There was no difference between the two groups when postoperative swelling was evaluated on the second day. From the third day, conversely, swelling decreased faster in Group 2 than in Group 1. Our data demonstrate that the use of the thermosetting gel containing doxycyclyne hylcate 3%, given as an intra-alveolar injection at the end of surgery, is effective in the prevention of postoperative symptoms after third molar extraction.The surgical removal of impacted third molars involves trauma to soft and bony tissue and can result in considerable pain, swelling, reddening and bleeding. These postoperative sequela can cause stress to the patient and affect the patient's quality of life after surgery. These sequelae can happen also after surgical-orthodontic treatments (1-3). Prediction of impaction of third molars in patients could be of great help in the planning of orthodontic treatment, surgery, or prostheses (4-8).The need for better discomfort control in patients who undergo third molar surgery is widely recognized, and several types of medications have been proposed (9). In order to improve the postoperative course, the surgical procedure must be appropriate and as far as possible non-traumatic; it is also useful to prescribe a suitable medication protocol.The aim ofthe antibiotic prophylaxis, is to protect the patient from the consequences of transient