Post-operative atrial fibrillation (POAF) is a common cause of morbidity and mortality after cardiac surgery. Although clinical risk factors exist, their accuracy is insufficient for widespread clinical use. We enrolled 98 adult patients scheduled for cardiac surgery. Clinical risk factors for POAF were assessed from a history and physical. Occurrence of POAF was observed prior to discharge. DNA methylation data was obtained from whole blood prior to surgery. Statistical significance of POAF was analyzed for every CpG after controlling for smoking, sex, ethnicity and cell type composition with ReFACTor and CEllFi. Four CpGs met genome wide significance for association with POAF after accounting for covariates and cell type composition with both ReFACTor and CEllFi. Two of these CpGs are within the promotor of ZFPM2. Further investigation is needed to validate this finding in a separate validation cohort and to elucidate the mechanism of ZFPM2 and its involvement in atrial arrhythmias.