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<title>Abstract</title> Background Treatment landscape of advanced soft tissue sarcoma (aSTS) has been rapidly evolving in recent decades. The impact of novel treatment approaches on the healthcare system is a complex issue that needs to carefully balance the potential benefits with their associated costs. In this retrospective study we accessed multiple large administrative datasets of publicly funded health systems to describe real-world healthcare resource use (HCRU) patterns and associated costs for managing patients with advanced soft tissue sarcoma in Australia. Methods Probalistic data linkage was performed using 361 patients with aSTS identified from a tertiary referral centre between January 1, 2010, and December 31, 2015, with four administrative datasets on hospital admission, emergency presentation, Medicare Benefits Schedule and Pharmaceutical Benefits Schedule. Two specific time settings were nominated to extract HCRU and to analyse costs: 12 months prior to the diagnosis of aSTS and 12 months post the diagnosis of aSTS. Comparison data were presented using descriptive statistics. Results The yearly cost per patient was AUD $42,622 before the aSTS diagnosis, increasing to AUD $69,145 after the aSTS diagnosis. The bootstrap confidence interval for the difference in all costs was AUD $24,982 (95% confidence interval (CI), $18,164 to $31,390), in excess of costs after the diagnosis of aSTS. The most substantial cost difference was driven by the inpatient care with the hospital admission costs accounting for up to 79%. The cost of subsidised medication only accounted for 1.3% of the total healthcare costs before aSTS diagnosis, rising to 5.2% after the diagnosis of aSTS. The overall cost was substantially higher for the group who received chemotherapy (AUD $39,160, 95% CI [$30,170 to $47,594] vs. AUD $13,057, 95% CI [$4,766 to $22,323]). Conclusions This is the first Australian study to use individual-level data in estimating the healthcare cost for patients diagnosed with aSTS. The healthcare costs are significant, predominantly driven by costs incurred from inpatient hospital care. These findings present an opportunity to inform the Australian healthcare system on the importance of optimising resources and adopting more efficient strategies for planning and delivering health services.