To conduct a comprehensive multivariate analysis of variables associated with deep sternal wound infection, after open-heart surgery via median sternotomy. A retrospective cohort of all adult patients, who underwent open-heart surgery at Odense University Hospital between 01-01-2000 and 31-12-2020 was extracted from the West Danish Heart Registry. Data were analyzed using maximum likelihood logistic regression. A total of 15,424 patients underwent open-heart surgery and 244 developed a deep sternal wound infection, equivalent to 1,58 %. After data review 11,182 entries were included in the final analysis, of which 189 developed DSWI, equivalent to 1,69 %. Multivariate analysis found the following variables to be associated with the development of deep sternal wound infection (odds ratios and 95%confidens intervals in parentheses): Known arrhythmia (1.70; 1.16-2.44), Left Ventricular Ejection Fraction (1.66; 1.02-2.58), Body Mass Index 25-30 (1.66; 1.12-2.52), Body Mass Index 30-35 (2.35; 1.50-3.71), Body Mass Index 35-40 (3.61; 2.01-6.33), Body Mass Index 40+ (3.70; 1.03-10.20), Age 60-69 (1.64; 1.04-2.67), Age 70-79 (1.95; 1.23-3.19), Chronic Obstructive Pulmonary Disease (1.77; 1.21-2.54), Reoperation (1.63; 1.06-2.45), Blood transfusion in surgery (1.09; 1.01-1.17), Blood transfusion in intensive care unit (1.03; 1.01-1.06), Known peripheral atherosclerosis (1.82; 1.25-2.61), Current smoking (1.69; 1.20-2.35), Duration of intubation (1.33; 1.12-1.57). Increased risk of deep sternal wound infection after open-heart surgery is a multifactorial problem, while some variables are unchangeable others are not. Focus should be on optimizing the condition of the patient prior to surgery e.g. weight loss and smoking. But also factors surrounding the patient e.g. preventing blood loss and minimizing intubation time.