Background: Intramedullary nailing is an accepted method of management for femoral diaphyseal fractures. There are, however, risks associated with surgery such as nonunion, infection, and venous thromboembolism (VTE). Objectives: Our objective was to identify independent predictors of complications following intramedullary nailing of femoral diaphyseal fractures in young adults. Patients and Methods: During a 3-year period, 59 patients (aged 13–55 years) underwent intramedullary nailing for high energy femoral diaphyseal fracture. These patients were identified from a radiographic database. Patient demographics, socioeconomic status, smoking status, alcohol intake, diagnosis of diabetes, intravenous drug use, fracture comminution, and if it was open were recorded retrospectively. Complications assessed were nonunion, deep infection, VTE, amputation, and revision of the nail. Results: Univariate analysis identified that socioeconomic status, excess alcohol intake, intravenous drug use, fracture comminution, and an open fracture were predictors of complications. Logistic regression analysis identified that intravenous drug use (P = 0.036) and open fractures (P = 0.05) were significant independent predictors of nonunion. There was a trend toward significance (P = 0.07) for excess alcohol intake as a predictor of deep infection. Fracture comminution (P = 0.015) was an independent predictor of VTE. Logistic regression analysis failed to identify any significant independent predictors of amputation or revision after adjusting for confounding variables. Conclusions: Intravenous drug use, open fractures, and fracture comminution are independent predictors of nonunion and/or VTE. These patient factors could be used to identify those at risk of nonunion and VTE who may benefit from early preventative measures.