Background: Ripretinib is a switch-control tyrosine kinase inhibitor (TKI) that broadly inhibits KIT and platelet-derived growth factor receptor α (PDGFRA) kinase signaling. Ripretinib demonstrated favorable therapeutic efficacy and safety in clinical trial settings and was approved for advanced GIST who have received prior treatment with three or more TKIs. Here, we report the efficacy and safety of ripretinib in Chinese patients with advanced GIST in a multicenter, retrospective study. Methods: Patients with advanced GIST who received ripretinib in ZheJiang province were included and analyzed. The primary endpoint was progression-free survival (PFS) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 GIST-Specific Standard. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of therapy (DOT), safety and overall survival (OS). Exploratory endpoint was the predominant genotype for ripretinib treatment. Results: 23 patients were enrolled, while 21 patients were included in the study. The median number of prior lines of therapy was 3 (range, 0-4). The site of primary tumor was predominantly the small intestine (52.38%) and 47.62% of patients with ECOG performance status≥2. Median PFS was 7.1 months (95% CI, 4.9-NA), the ORR and DCR were 9.52% and 85.71%, respectively. Median duration of therapy was 7.3 months (range, 1.8-12). For patients on ≥fourth-line therapy, the median PFS was 9.2 months (95% CI, 4.6-NA), the ORR and DCR were 7.14% and 100%, respectively. Shorter interval between the end of the latest TKI and ripretinib therapy was correlated with longer median PFS and OS (P = 0.021 and P = 0.009, respectively). In univariate analysis, patients with KIT exon 9 mutation had a shorter PFS than patients without KIT exon 9 mutation (hazard ratio, 3.692; 95% CI, 1.109 to 12.294; P = 0.033). Patients with KIT exon 17/18 mutation had a longer PFS (hazard ratio, 0.097; 95% CI, 0.011 to 0.871; P = 0.037). Ripretinib was associated with a favorable safety profile, grade 3 treatment-emergent adverse events (TEAEs) were recorded in 5 patients. No grade 4 or 5 TEAEs were recorded. Conclusions: The ECOG performance status of the patients that received ripretinib in this study is poor. Ripretinib can provide clinical benefit in advanced GIST in real-world China with a favorable safety profile. Immediately switch from the latest TKI to ripretinib after progression will prolong the survival of the patients.