Aim. Preoperative serum CRP has been identified as an independent predictor in various malignancies. For osteosarcoma, however, the value of serological markers is unreliable. Aim of this study was to evaluate the prognostic power of preoperative CRP in patients with osteosarcoma. Method. Out of our prospective database, 87 patients with osteosarcoma (43 female, 44 male with an average age of 20.4 years) have been identified with complete documentation of peri-operative CRP-levels, a minimum two year follow-up and after exclusion of concomitant infection, smoking-history or cardio-vascular disease. Pre-operative CRP before tumour resection was correlated with clinical and pathological factors, overall survival and infection rates in an uni- and multi-variate statistical model with and without landmark analysis. Results. Mean pre-operative serum CRP was 0.73mg/dL (range 0.0 to 8.5) and significantly correlated with overall survival, age at time of operation and histological subtype, but not with sex, tumour grading, response to chemotherapy, recurrent disease or post-operative infection in uni-variate analysis. Patients with CRP <1mg/dL had a five year overall survival of 70% compared to 43% for patients with CRP >1mg/dL (p=0.023). In multi-variate analysis both age and pre-operative CRP had an independent significant influence on overall survival. The hazard ratio for patients with elevated levels of CRP was 1.252. In a subgroup analysis of 60 patients with endoprosthetic replacement, pre-operative CRP was no significant predictor for deep prosthetic infection and infection was no significant predictor for overall survival with and without landmark-analysis though patients with infection showed lower levels of CRP. However, this difference was not significant. Conclusion. Pre-operative serum CRP is an independent prognostic factor for overall survival of patients with osteosarcoma, but not for infection. Its role in predicting response to established chemotherapies, as well as the controversially discussed impact of infection on survival will remain subject of multi-centre investigations