Postoperative pain management after total knee arthroplasty (TKA) remains a great challenge even today. In the context of new fast-track concepts, the importance of multimodal therapies for the effective treatment of pain and the reduction of side effects, as well as for the rapid ambulation of patients is increasing. Therefore, new continuous intra-articular catheter-systems (IAC) are under investigation. A total of 120 patients receiving total knee replacement were included in a prospective randomized comparative study. In a standardized treatment regime 60 patients received an IAC (group A), while in 60 patients a continuous femoral nerve block (FNB) was applied (group B). All other perioperative therapy components were identical for all patients. In the first 5 days after surgery pain intensity (VAS), passive and active flexion, opioid requirements, and self-initiated or hallway ambulation were investigated and documented. The initiation time, operation time, and length of hospital stay were recorded. Regarding pain intensity no significant differences occurred (mean 5.1 +/- 2.5 vs. 4.6 +/- 2.6; p = 0.27). Also, additional opioid requirements and range of motion (ROM) showed no relevant distinctions of therapy. In the IAC group a much more rapid independent mobilization was achieved (p < 0.001). The mean initiation time before surgery decreased markedly compared to the FNB group by 11.9 min (p < 0.001). With respect to the operation time and duration of hospital stay there was no noticeable difference. The failure rate and the rate of dislocation of FNB appear to be increased. The perioperative treatment with an IAC system is an easy technique, which ensures a markedly faster ambulation following TKA compared to the treatment with continuous FNB. Hence, its usage, especially in fast-track concepts can be recommended. In this study, a comparison of pain intensity, the additional requirement of opioids and early range of motion (ROM) offers no benefits compared to FNB. Due to time savings cost reduction can be achieved.