The occurrence and risk factors for adverse clinical events associated with cemented long-stem femoral arthroplasty were studied. The hypothesis was that patients with femoral metastatic disease and previously uninstrumented canals were at higher risk for such adverse events. Fifty-five consecutive patients requiring long-stem femoral arthroplasty at two institutions were retrospectively reviewed. Adverse clinical events including hypotension, sympathomimetic administration, and O2 desaturation were subclassified according to the timing of their occurrence. Adverse events occurred in 34 of 55 patients (62%), including coma in two patients and death in a third patient. The three catastrophic events occurred in patients with metastatic disease involving previously uninstrumented femoral canals. Desaturation was more frequent in patients with metastatic disease and previously uninstrumented canals compared with patients who had revision arthroplasty and patients with previously instrumented femoral canals. Preexisting medical illness was a significant risk factor in total adverse clinical events that included cement-associated adverse clinical events and cement-associated and postoperative hypotension. In long-stem cemented femoral components risk factors for adverse clinical events included metastatic disease, uninstrumented femoral canals, and preexisting medical conditions. These findings underscore the importance of appropriate patient selection, patient and family education, and anesthesia preparation before long-stem cemented femoral arthroplasty.