Background New-onset postoperative atrial fibrillation (POAF) is common after cardiac surgery. Early identification of its risk factors during the preoperative period would help in reducing the associated morbidity, mortality, and healthcare costs. Aim of the study This study aimed to identify the predictors of POAF following open cardiac surgery, with emphasis on biochemical parameters. Methods A total of 1191 patients with no preoperative atrial fibrillation (AF) and undergoing open cardiac surgery for any reason were included in this retrospective study. Data on clinical and biochemical parameters, the occurrence of new-onset AF, and its clinical course were retrieved from the hospital database. Results During the early postoperative period 330 patients (27.7%) developed atrial fibrillation, at median third postoperative day (range 1-6 days) and 217 (65.8%) responded to treatment. Multivariate analysis identified the following as the significant independent predictors of any POAF: EF < 60% (Odds ratio (OR), 2.6), valvular intervention (OR, 2.4), liver failure (OR, 2.4), diabetes (OR, 1.6), low hematocrit (OR, 2.1), low thrombocyte (OR, 5.6), low LDL (OR, 1.6), high direct bilirubin (OR, 2.0), low GFR (OR, 1.6), and high CRP (OR, 2.0). Following parameters emerged as significant independent predictors of persistent AF: EF < 60% (OR, 1.9), diabetes (OR, 2.1), COPD (OR, 1.8), previous cardiac surgery (OR, 3.1), valvular intervention (OR, 2.4), low hematocrit (OR, 1.9), low LDL (OR, 2.1), high HbA1c (OR, 2.0), and high CRP (OR, 2.7). Conclusions Certain parameters assessed during preoperative physical and laboratory examinations have the potential to be used as markers of POAF.