Dry socket (DS) is a very common post-extraction complication. Pain is the most important clinical symptom in DS. Although many studies provided variant treatment methods for pain alleviation, there is still a wide controversy about their efficacy. Ozone achieved promising results in the treatment of variant conditions including DS due to its powerful oxidation and metabolism enhancement capacity, however, no enough data is available in the literature about its efficacy in DS treatment; particularly the comparative studies. In the current comparative study, forty patients with DS were randomly divided into two equal groups. In Group I, a brief saline irrigation of the extraction socket was followed by ozone major autohemotherapy (AHT) which was performed by withdrawing a venous blood to be ozonized; and then being reinfused into the vain. A cotton pellet impregnated with Oleozon was lightly packed in the socket after a brief saline irrigation in group II patients. Oleozon was more effective than AHT regarding the required total treatment period and the number of the required analgesic tablets. Oleozon might have an increased capacity of oxygen delivery to the ischemic tissues than AHT. This might provide an evidence for the ischemic etiology of the dry socket development.