Background. Pazopanib is an oral angiogenesis inhibitor approved to treat soft tissue sarcoma (STS) but associated with large interpatient pharmacokinetic (PK) variability and narrow therapeutic index. In order to improve its clinical use, this study aimed to define specific threshold of pazopanib trough concentration (Cmin) associated with better progression free survival in STS patients. Methods. In this observational study, pazopanib Cmin was monitored over the treatment course. For the primary endpoint, the 3-month PFS in STS was analyzed with logistic regression. Secondary, we performed exposure–overall survival (OS) in STS (Cox model plus Kaplan–Meier analysis/ log-rank test) and exposure-toxicity analyses. Results. One hundred eighteen patients (95 STS and 23 BS) were eligible for PK/PD assessment. In multivariable analysis, pazopanib Cmin < 27 mg/L was independently associated with a risk of progression at 3 months (OR 4.21, 95% CI [1.47-12.12], p = 0.008). OS was not statistically longer between patients with Cmin > 27 mg/L and those with Cmin < 27 mg/L (log-rank p = 0.07). A higher average of PAZ Cmin over the first 3 months of treatment was associated with a higher risk of grades 3-4 toxicities (40.0 vs 30.5 mg/L (OR 1.05, IC95 [1.01-1.09], p = 0.01) Conclusion. Pazopanib Cmin ≥ 27 mg/L was independently associated with improved 3-month PFS in a large cohort of STS patients. Pharmacokinetically-guided dosing could be helpful to optimize clinical management of STS patients in daily clinical practice.