In an unselected, prospective case control study, the incidence of risk factors and perioperative complications was investigated in 237 knees (203 patients) undergoing implantation of cementless total knee endoprostheses. Intraoperative complications and postoperative complications occurred in 84 patients (99 knees), with 61 specific orthopaedic complications in 50 patients (57 knees) and 74 nonsurgical complications in 55 patients (65 knees). The presence of cardiac, neurologic, or psychiatric concomitant diseases, advanced age, male gender, high-risk anesthesia scores, number and extent of intraoperative blood pressure fluctuations, and surgery under intubation anesthesia are associated significantly with the incidence of nonsurgical perioperative complications. In contrast, body weight, concomitant metabolic and circulatory diseases, previous surgery on the joint, origin of the articular disease, and the duration of surgery and tourniquet time do not correlate with the probability of a nonsurgical perioperative complication. A significant correlation with the parameters investigated could not be found for the occurrence of specific orthopaedic complications. The current report identifies specific risk factors that define patients with risk of having perioperative complications according to objective criteria. These parameters must be given individual consideration when establishing the indication and planning of surgery.