INTRODUCTION Pathologic fractures often contribute to adverse events in metastatic bone disease, and prophylactic fixation offers to mitigate their effects. This study aims to analyze patient selection, complications, and in-hospital costs that are associated with prophylactic fixation compared with traditional acute fixation after completed fracture. MATERIALS AND METHODS The Nationwide Inpatient Sample database was queried from 2002 to 2014 for patients with major extremity pathologic fractures. Patients were divided by fixation technique (prophylactic or acute) and fracture location (upper or lower extremity). Patient demographics, comorbidities, complications, hospitalization length, and hospital charges were compared between cohorts. Preoperative variables were analyzed for potential confounding, and x2 tests and Student’s t tests were used to compare fixation techniques. RESULTS Cumulatively, 43,920 patients were identified, with 14,318 and 28,602 undergoing prophylactic and acute fixation, respectively. Lower extremity fractures occurred in 33,582 patients, and 10,333 patients had upper extremity fractures. A higher proportion of prophylactic fixation patients were white (P = .043), male (P = .046), age 74 years or younger (P, .001), and privately insured (P, .001), with decreased prevalence of obesity (P = .003) and/or preoperative renal disease (P = .008). Prophylactic fixation was also associated with decreased peri- and postoperative blood transfusions (P, .001), anemia (P, .001), acute renal failure (P = .010), and in-hospital mortality (P = .031). Finally, prophylactic fixation had decreased total charges (2$3,405; P = .001), hospitalization length (P = .004), and extended length of stay (greater than 75th percentile; P = .012). CONCLUSION Prophylactic fixation of impending pathologic fractures is associated with decreased complications, hospitalization length, and total charges, and should be considered in appropriate patients.