Background: Globally, greater than 90% of infections in the head and neck region are of odontogenic origin. Several species of bacteria present in the mouth that exploit the circumstances of human immunity and oral hygiene to cause infections which can spread to the facial region, neck and to the rest of the body leading to serious outcome. Various bacteriological studies show variations in their conclusion. Objective: The aim of this study was to provide evidence of the most prevalent organisms involved in orofacial space infections and the most effective antibiotics for maxillofacial odontogenic infection (OMI). Material and methods: Sixty patients clinically diagnosed as OMI were enrolled in this study selected from different polyclinics from dental department at Jeddah area, Saudi Arabia. The mean age of patients was 31.4±17.26 year (35 males and 25 females). Inclusion criteria were patients with maxillofacial infections that assessed radio-graphically using periapical or panoramic views and patients had swelling intra-oral and/or extra-oral, fistula, redness, trismus, and lymphadenopathy. Exclusion criteria included patients already on antibiotics and medically compromised patients (diabetic, hepatitis, and HIV+). Results: The most commonly involved facial space was the combination of buccal and submandibular space that was involved in 46.67% of patients. While, among the entire aerobically cultured bacteria, Ciprofloxacin and Amoxicillin/clavulanic acid were the most sensitive drug with 97% and 95% of sensitivity respectively, followed by Clindamycin 88% and Cefotaxime (80%). The least effective drug was amoxicillin 18% (Table 4). While, among the entire anaerobically cultured bacteria, Metronidazole was the most sensitive drug (93%) followed by Ciprofloxacin, Amoxicillin/clavulanic acid and Clindamycin with 90%, 87% and 85% of sensitivity respectively, where Cefotaxime was 78%. Conclusion: Maxillofacial odontogenic infection (OMI) is usually poly-microbial, consisting of a complex mixture of both anaerobes and aerobes. Ciprofloxacin, Amoxicillin/clavulanic acid and Clindamycin were the most effective drugs for all isolates of OMI and the least effective drug was amoxicillin of OMI. Early surgical intervention along with selective antibiotics can stop these infections spread to deeper spaces of face and neck and hence many untoward complications can be avoided.