There is a lack of understanding of risk factors and postoperative outcomes of syndesmotic injuries with singular versus multipart fractures. A retrospective analysis was done between 2008 and 2016, utilizing the American College of Surgeons National Surgical Improvement Program database. Patients with open reduction and internal fixation of isolated lateral malleolus fractures, bimalleolar fractures, or trimalleolar fractures were identified. A total of 2045 patients underwent syndesmotic fixation. Subjects with bimalleolar or trimalleolar fractures were more likely than those with unimalleolar fractures to be Caucasian (odds ratio [OR] = 1.5 and 1.9), female (OR = 1.8 and 2.9), aged > 65 years (OR = 1.6 and 1.9), or have American Society of Anesthesiologists (ASA) classification III (OR =1.5 and 1.4) (all, P ≤ 0.028). Patients with a unimalleolar fracture were more likely than those with a bimalleolar or trimalleolar fracture to be male (OR = 1.8 and 2.9), African American (OR = 1.5 and 1.8), aged < 30 years (OR = 1.4 and 1.8), or present with an ASA I classification (OR = 1.6 and 2.0) (all, P ≤ 0.004). Subjects with bimalleolar or trimalleolar fractures were more likely than those with unimalleolar fractures to have lengthier hospital stays (OR = 1.8 and 2.1), while patients with trimalleolar fractures were more likely than those with unimalleolar fractures to have hypoalbuminemia (OR = 2.3), develop a complication (OR = 2.2) or an open wound (OR = 1.9), or to be readmitted (OR = 2.2) (all, P ≤ 0.036). In this study, comorbidity rates and adverse postoperative outcomes significantly increased as the number-part fractures increased in syndesmotic fixation patients. Risk factors also varied across fracture severity.