The coronary sinus reducer (CSR) has been introduced as therapy for patients with refractory angina with no other treatment options. Aim of this study is to investigate the efficacy of the CSR in patients with refractory angina and presence of coronary chronic total occlusions (CTO). In this multicentre, international retrospective study, patients undergoing CSR implantation were screened and divided in 2 groups according to the presence/absence of CTO lesions. Baseline and clinical characteristics were analyzed in the 2 groups. Primary-outcome consisted of the variation in Canadian Cardiovascular Society (CCS) class at 6-month follow-up. Between January 2014 and December 2018, 205 patients with refractory angina were consecutively treated with the study device in the participating centers, 103 (50.2%) of which had a CTO lesion at coronary angiogram and formed the CTO-group. Baseline characteristics of the study population were well balanced between the 2 groups. CSR was successfully implanted in all cases. Baseline CCS class was 3 ± 0.5 in the CTO-group versus 3.1 ± 0.6 in the non-CTO group (p = 0.45), and improved at follow-up to 1.6 ± 0.9 versus 2 ± 1.1 respectively (p <0.01), with a significantly higher improvement in CCS class in the CTO-group (1.4 ± 0.9 vs 1.1 ± 1 respectively, p = 0.01). Any improvement in CCS class was registered in 79 (80.6%) CTO-patients, while a significantly lower percentage (65 patients, 66.3%) of the non-CTO patients reported benefits in CCS class (p = 0.03). In conclusions, patients suffering from refractory angina with non-revascularized CTO lesions have a better response to CSR implantation than patients without CTOs. CSR implantation should be considered a valid complementary therapy to CTO-PCI in these patients.