Background: Neo-adjuvant CT with anthracyclines plus ifosfamide (AI) is a therapeutic option in patients (pts) with marginally LASTS, aiming at a local benefit, facilitating surgery, in addition to the systemic one (ESMO guidelines 2017). Methods: We retrospectively reviewed all consecutive pts with LASTS who received AI (doxorubicin 60 mg/m2 plus ifosfamide 9g/m2) regimen treated from 1996 to 2015 in neo-adjuvant setting in our institution. Clinical, biological, imaging and pathology data were collected from patient files. Survival curves were calculated according to Kaplan-Meier and compared with the log-rank test or a Cox proportional hazard model, using R 3.4.3. Results: The data of 161 pts (89 males, 72 females) was collected. The median age was 45 years and the median tumor size was 10 cm (range 3-27 cm). LASTS were located in the extremities (67%), trunk (17%) and retroperitoneal (8%). The main histotypes were UPS 73 (45%), L-sarcomas 36 (23%), and synovial sarcoma 26 (16%). Fifty-eight % of pts had a grade 3, 38% a grade 2 and 4% a grade 1 disease. The median number of cycles of CT administered was 3 (range 1-6). The clinical benefit rate was 87 % pts (49.5%) (partial response and stable disease according to RECIST). All patients were subsequently operated, including 5 amputations, 85% R0 and 15% R1 resections. Eighty percent of pts received adjuvant radiation therapy and 10% received adjuvant CT. Twenty-one pts experienced a local relapse and 48 developed distant metastases. After a median follow-up of 57 months, the 5-yr-DFS was 56% (CI 95% [47-65]) and the 5-yr OS was 70% (CI 95% [61-79]) . There was a quasi-linear significant relationship between the rate of residual identifiable cells (RIC) and both DFS and OS, with the most discriminating cut-off being 35% (respectively for OS and DFS, p = 0.012 and p = 0.0054); each additional percent worsening the prognosis. Grade was correlated to a good histologic response (p = 0.00019). A R0 resection was significantly related to a better DFS (p = 0.025) with a trend on OS (p = 0.058). Conclusions: Neo-adjuvant CT with AI regimen in LASTS facilitates surgery, with a R0 resection achieved in 85% of pts. The rate of RIC correlates to outcome.