Objective To investigate the risk factors of surgical site infection ( SSI) in adult patients undergoing major heart surgery, and to provide the reference of controlling the development of SSI. Methods A case-control study was conducted with 54 SSI patients underwent major heart surgery from January 2001 to December 2009 in the case group and 162 controls in the control group. Univariate and multivariate conditional logistic regression analysis were used to analyse the risk factors of SSI development Results Univariate conditional logistic regression showed the risk factors for the development of SSI were left ventricular ejection fraction ( LVEF) < 50% (odds ratio ( OR) = 2.134,95% C/: 1.095 - 4. 159, P = 0. 026) , heart function New York Heart Association classification (NYHA) ≥Ⅲ grade, (OR =2. 390,95% CI: 1. 218 -4. 690; P = 0. 011) .diabetes (OR=3.275, 95% CI: 1.391 - 7. 708; P = 0.007), chronic obstructive pulmonary disease (COPD) ( OR = 5. 408,95% CI: 1.248- 23.445,P = 0.024),extracorporeal circulation time>90 mins ( OR =3. 045,95% CI: 1.540 - 6.024, P = 0. 001 ) , operation time > 4 h ( OR = 3. 281, 95% CI: 1. 610 - 6. 685, P = 0.001 ) , blood product consumption >2 u ( OR = 1. 929,95% CI; 1. 018 -3. 675;P =0. 044) .incision continuous suture close ( OR = 2.344,95%CI: 1.221 -4.498;P =0.010) exploration for bleeding (OR =6. 625,95%CI: 1.597-27.491 ;P =0. 009) , postoperative hyperglycemia (OR = 3. 510,95%CI:l. 5% -7. 718;P =0. 002) ,the stay in intensive care units (ICU) > 72 h ( OR = 3. 281,95% CI: 1. 505 - 7. 150;P = 0. 003). Multivariate analysis showed 3 variables increased with the risk of SSI: operation time >4h (OR = 3. 100,95% CI: 1.470 - 6. 537,P = 0.003 ) , incision continuous suture close (OR =2. 340,95% CI: 1. 183 - 4. 692, P = 0. 015 ) , and postoperative hyperglycemia (OR = 3. 272,95% CI:1.427 -7. 505,P=0. 005 ). Conclusions This study shows that the operation time >4 h, incision continuous suture close and postoperative hyperglycemia are risk factors most likely associated with SSI development in major heart surgery.