OBJECTIVES: Risk prediction in adult patients undergoing cardiac surgery remains inaccurate and should be further improved. Therefore, we aimed to identify risk factors that are predictive of mortality, stroke, renal failure and/or length of stay after adult cardiac surgery in contemporary practice. METHODS: We searched the Medline database for English-language original contributions from January 2000 to December 2011 to identify preoperative independent risk factors of one of the following outcomes after adult cardiac surgery: death, stroke, renal failure and/or length of stay. Two investigators independently screened the studies. Inclusion criteria were (i) the study described an adult cardiac patient population; (ii) the study was an original contribution; (iii) multivariable analyses were performed to identify independent predictors; (iv) ≥ 1 of the predefined outcomes was analysed; (v) at least one variable was an independent predictor, or a variable was included in a risk model that was developed. RESULTS: The search yielded 5768 studies. After the initial title screening, a second screening of the full texts of 1234 studies was performed. Ultimately, 844 studies were included in the systematic review. In these studies, we identified a large number of independent predictors of mortality, stroke, renal failure and length of stay, which could be categorized into variables related to: disease pathology, planned surgical procedure, patient demographics, patient history, patient comorbidities, patient status, blood values, urine values, medication use and gene mutations. Many of these variables are frequently not considered as predictive of outcomes. CONCLUSIONS: Risk estimates of mortality, stroke, renal failure and length of stay may be improved by the inclusion of additional (non-traditional) innovative risk factors. Current and future databases should consider collecting these variables.