Aim To compare the long-term clinical efficacy and safety of hybrid surgery and PCI in the treatment of coronary heart disease in patients with multivessel disease. Methods A prospective randomized controlled study was adopted from 2012 January to 2014 June, 102 cases in our hospital, in the diagnosis of coronary angiography for multivessel coronary artery disease, randomly divided into hybrid group （n53） and PCI group （n49）, patients accepted hybrid surgery in hybrid group, patients with multi branch coronary artery lesions accepted pure PCI treatment in PCI group. 2-years follow-up was after 1, 3, 6, 9 and 12 month. After 12 months, coronary angiography was adopted to evaluate target vessel patency rate and SYNTAX score. Clinical status of patients, and the primary and secondary end points, the rate of long term survival and cardiovascular adverse events were recorded. Results The amount of contrast agent of hybrid group was lower than that of PCI group （P<0.05）. There was significantly difference of average hospitalization days, total stent length, postoperative hs-CRP peak of the two groups （P<0.05）. The hospital adverse events of contrast-induced nephropathy, acute heart failure, recurrent angina pectoris and postoperative hypotension were significant different in the two groups （P<0.05）. There was no significant difference of repeat myocardial infarction, target vessel revascularization, cerebrovascular accident and death in the two groups （P>0.05）. All patients were followed for a median of 2.4 years follow-up, with an average of 16.2 ± 11.3 months. Between the two groups, there was remarkable difference of repeat myocardial infarction, target vessel revascularization, acute heart failure, recurrent angina pectoris （1.9% vs. 8.2%, 1.9% vs. 8.2%, 3.8% vs. 12.2%, 5.7% vs. 14.3%, P0.023）. 2-years total mortality was 3.8% in hybrid group, and 4.1% in PCI group. In the two groups, 1-year target vessel patency rate and SYNTAX scores were statistically significant （P<0.05）. Conclusions Compared with PCI treatment, coronary hybrid surgery can reduce adverse events in patients with multivessel disease in the long-term, and operation safety was high.