Background - There is clear evidence that patients having coronary artery bypass graft surgeries with an internal mammary artery (IMA) have better long-term survival. Some studies have suggested a short-term protective effect as well but, because older and sicker patients are less likely to receive an IMA graft, there has been concern that the apparent protective effect of the IMA on short-term mortality has been confounded by other risk factors. This study was intended to examine the independent effect of IMA grafts on in-hospital mortality while adjusting for patient and disease factors. Methods and Results - We studied the use of the left IMA (LIMA) in 21 873 consecutive, isolated, first-time coronary artery bypass graft procedures from 1992 through 1999. A total of 87% of the patients received a LIMA graft. LIMA graft use was associated with a significantly decreased risk of mortality. The crude odds ratio for death (LIMA versus no LIMA) was 0.26 (95% confidence intervals, 0.22, 0.31; P<0.001). LIMA grafts were protective across all major patient and disease subgroups. The odds ratios by subgroup ranged from 0.13 to 0.48. After adjustment for all major risk factors, the odds ratio for death was 0.40 (95% confidence intervals, 0.33, 0.48; P<0.001). Rates of cerebrovascular accident, return to cardiopulmonary bypass, return to the operating room for bleeding, and mediastinitis or sternal dehiscence requiting surgery were also less in the LIMA group, although not significantly so. Conclusions - These data suggest that in addition to its well-documented patency and long-term beneficial effect, LIMA grafting has a strong protective effect on perioperative mortality.