Objective: To explore the relationship between coronary tortuosity and coronary microvascular disease (CMVD). Methods: Patients with typical angina symptoms and without serious coronary artery stenosis by coronary angiography were enrolled from June 2014 to December 2016, and CMVD was diagnosed by single photon emission tomography (SPECT). According to the SPECT results, patients were divided to the CMVD group and non-CMVD group. The baseline clinical characteristics, results of coronary angiography were compared between the two groups. The logistic analysis was used to analyze the relationship between coronary tortuosity and CMVD. Result: A total of 117 cases were enrolled, with 69 cases in the CMVD group and 48 cases in the non-CMVD group. No differences were found in gender distribution, age, hypertension, lipid abnormality, hyperuricemia and uses of statins between the two groups (all P>0.05). Incidence of diabetes (78.26%(54/69) vs. 35.42% (17/48) , P<0.05), hs-CRP ((4.29±2.15)mmol/L vs. (2.63±1.20)mmol/L, P<0.001), LDL-C ((2.98±0.96)mmol/L vs. (2.52±0.83)mmol/L, P=0.008) and homocysteine ((13.7±5.61)mmol/L vs. (11.5±4.38)mmol/L, P=0.025) levels were higher in the CMVD group than in the non-CMVD group. The data derived from echocardiographic examination were similar between the two groups. The Corrected TIMI frame counts were higher in the CMVD group than in non-CMVD group (LAD: 31.56±4.92 vs. 27.31±3.75, LCX: 29.47±4.18 vs. 26.62±3.19, RCA: 29.09±5.05 vs. 26.24±3.28, all P<0.001). The incidences of coronary atherosclerosis (76.81% (53/69) vs. 27.08% (13/48) , P<0.001) and coronary tortuosity ( (60.87% (42/69) vs. 33.33% (16/48) , P=0.035) were also higher in the CMVD group than in non-CMVD group. Logistic analysis found that coronary tortuosity (OR=6.111, 95%CI 2.707-13.794, P<0.001), diabetes (OR=6.565, 95%CI 2.883-14.948, P<0.001) and coronary atherosclerosis (OR=8.918, 95%CI 3.822-20.808, P<0.001) were independent risk factors of CMVD. Conclusion: Coronary tortuosity, diabetes and coronary atherosclerosis are related to CMVD in this patient cohort.