Odontogenic space infections are a common presentation in oral and maxillofacial surgery units worldwide. Multiple patient and treatment dependent variables may be used predict the outcomes of the disease process. This study was aimed at a retrospective evaluation of significant predictors of prognosis in terms of length of hospital stay and the need for re-exploration in cases of odontogenic space infections. Patients who underwent incision and drainage of odontogenic space infections were identified from the hospital records of the Department of Oral and Maxillofacial Surgery, College of Dental Sciences, Davangere, Karnataka, India. The variables assessed included Diabetic status, pyrexia on admission, topical rubefacient agent application, hot fomentation, recent tooth extraction, trismus, dysphagia or dyspnea on presentation, white blood cell count, number of spaces involved, antibiotics used, organisms isolated, severity of the infection and the anesthesia technique used (local anesthesia [LA], conscious sedation or general anesthesia). The sample consisted of 259 patients (110 male, 159 female) with a mean age of 41±16.9 years. Space infections were preceded by tooth extractions in 53 (20%) cases, rubefacient balm application in 130 (40%) and hot fomentation in 58 (22%) cases. Trismus was noted in 140 patients with an average mouth opening of 21±10.3 mm. Dyspnea and dysphagia were noted in 55 (21%) and 96 (37%) patients each. Sixty-six patients were diabetic. The average length of hospital stay was 5.8±3 days and re-exploration was required in 75 (29%) patients. Significant predictors of hospital stay were severity (P<0.001), number of spaces affected (P<0.001), hot fomentation (P=0.04), trismus (P<0.001), dysphagia (P<0.001) and dyspnea (P<0.001). Predictors of re-exploration are an increased primary surgery under LA (P<0.001), white blood cell count (P<0.001), rubefacient balm application (P=0.045), dysphagia (P<0.001), dyspnea (P=0.018), and reduced mouth opening (P<0.001). No significant correlation between diabetes and length of hospital stay or the need for re-exploration were found in this study. Poorer outcomes can be predicted based on the severity of the infection, the number of spaces involved, an increased white blood cell count as well as clinical signs and symptoms like trismus, dysphagia and dyspnea. Hot fomentation and Rubefacient agent application were identified as significant determinants of poor prognosis in this study. The presence of these indicators warrants a more aggressive approach towards management of space infections.