Objective: To determine the evidence for use of ranolazine for treatment and prevention of postoperative atrial fibrillation (POAF) in patients undergoing cardiac surgery. Data Sources: A literature search of MEDLINE (1946 to January 2014) was conducted, using the search terms ranolazine, atrial fibrillation, and cardiac surgery. A search of reference citations was conducted to identify additional references. Study Selection and Data Extraction: Clinical trials investigating the use of ranolazine for POAF were included in the review. Data Synthesis: Three clinical trials were reviewed; 2 trials, 1 retrospective and 1 prospective, compared ranolazine with amiodarone or usual care for prevention of POAF and demonstrated a significant decrease in the incidence of POAF without increasing the incidence of postoperative complications. A third prospective trial used ranolazine in combination with amiodarone for the treatment of POAF and demonstrated a significant reduction in the time required to convert patients from atrial fibrillation to normal sinus rhythm compared with amiodarone alone. Conclusions: In these current small trials, ranolazine appears to be a safe and efficacious therapeutic alternative for the treatment and prevention of POAF in patients undergoing cardiac surgery. However, larger randomized controlled trials are needed before ranolazine should be considered for the treatment or prevention of POAF. It is an attractive option compared with current treatments for this indication—primarily β-blockers and amiodarone—because ranolazine has minimal effects on heart rate and blood pressure.