Background: Although the advent of antibiotics and improved dental care decreased the incidence and mortality, deep neck infections (DNIs) are not uncommon and present a challenging problem due to the complex anatomy and potentially lethal complications that may arise. Objectives: This study reviews our experience with DNIs and tries to identify the predisposing factors of life-threatening complications. Methods: A retrospective review was conducted of patients who were diagnosed as having DNIs in the Department of Otolaryngology and in the Department of Infectious Diseases at Treviso Regional Hospital from 1995 to 2003. Associations between life-threatening complications and other factors were determined by χ2 test, Fisher’s exact test and Student’s t test as appropriate. Results: One hundred sixty-seven charts were recorded; 95 (56.9%) were men, and 72 (43.1%) were women, with a mean age of 49.6 ± 20.4 years (range: 2–96). There were 39 patients (23.4%) who had associated systemic diseases, with 53.8% (21/39) of those having diabetes mellitus. The lateral pharyngeal and submandibular spaces were the most commonly involved spaces. Upper airway infections and odontogenic infections were the two most common causes of DNIs (47.5 and 27.9% of the known causes, respectively). The pathogenesis remained unknown in 45 patients (26.9%). Coagulase-negative staphylococcus (36.9%) and Streptococcusviridans (28.8%) were the most common organisms, identified through cultures. Of the abscess group (77 patients), 42 patients (54.5%) underwent surgical drainage under general anesthesia. Thirty-one patients (18.6%) developed life-threatening complications: airway obstruction (n = 18), descending mediastinitis (n = 6), jugular vein thrombosis (n = 4), and pneumonia (n = 3). Compared with other patients, the unique features of patients with life-threatening complications were as follows: older age (p = 0.04), a higher white blood cell count (p = 0.01), abscess formation (p = 0.02), associated systemic disease (p < 0.001), diabetes mellitus (p < 0.001), anterior visceral space involvement (p < 0.001), and multiple-space involvement (p < 0.001). Conclusions: DNIs continue to occur and these are associated with significant morbidity and mortality even in this era of antibiotics. Furthermore, the widespread and inappropriate use of antibiotics may change the clinical presentation and course of these infections, making them more elusive and less predictable also in complicated cases. The clinical assessment of patients who are older, with abscess formation, underlying systemic diseases, diabetes mellitus, visceral anterior space or multiple-space involvement requires careful consideration of potential complications.