Background: Our study assessed outcomes and factors predicting survival following initiation of multi-modality therapy for marginally inoperable STS patients (pts). Methods: A retrospective review of sequential pts deemed to have marginally inoperable STS at our tumor board was conducted. All pts must have had chemotherapy with the intention to be followed by radiation and surgery. Relapse free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The influence of disease characteristics and treatment on outcome was assessed using Cox regression. Results: Fifty- two pts (median age of 53) were included. Main histological subtypes were leiomyosarcoma (25%), liposarcoma, and synovial sarcoma (23% each). Disease was confined to extremity in 14 pts (27%), thorax in 8 (15%), abdo-pelvis in 25 (48%), and in combined locations in 5 (10%). All pts had doxorubicin/ifosfamide chemotherapy (mean cycle no. = 4.0). Six pts (11.5%) had progression during chemotherapy and did not undergo radiation or surgery. Nine patients (17.3%) underwent chemotherapy and surgery without radiation due to significant response with chemotherapy or concerns about radiation toxicity. Three patients (5.8%) underwent chemotherapy and radiation without surgery due to persistent unresectability of the tumour. The final 34 patients (65.4%) underwent both radiation and surgery after chemotherapy. Overall, 43 pts (83%) had surgery, negative margins were achieved in 41 (79%). With a median follow up of 26 months, median OS and RFS was 52 and 26 months respectively. Extremity location predicted superior RFS (HR 0.19, p = 0.009), and OS (HR 0.22, p = 0.02). The absence of radiotherapy predicted inferior RFS (HR 0.26, p = 0.005) and histology had significant effect on RFS (p = 0.04) with dedifferentiated liposarcomas having the worse outcome whereas synovial sarcomas having a more favorable outcome. Conclusions: Multimodality approach results in successful resection in most pts with marginally inoperable STS. Extremity location has a favorable impact on RFS and OS, while administration of radiotherapy and histological subtypes were predictors of RFS in our series.