To evaluate the role of prophylactic high-dose atorvastatin for prevention of postoperative atrial fibrillation (POAF), inflammatory response attenuation, and myocardial protection after valve replacement cardiac surgery. Randomized controlled trial. Assiut University Hospitals. Sixty-four adult patients undergoing cardiac valve replacement surgery. The participants were equally divided into 2 groups. Group S received 80 mg of atorvastatin (oral tablets), 12 and 2 hours preoperatively, and on the 2nd, 3rd, 4th, and 5th postoperative days. Control group C received placebo at the same time periods. The incidence of POAF, postoperative white blood cell count, serum C-reactive protein, interleukin 6, and troponin I. Group S patients showed a lower incidence of POAF compared with the placebo group (p = 0.031). The white blood cell count showed significant reductions in group S compared with group C on the second, third, fourth, and fifth postoperative days. The C-reactive protein level showed significant reductions on the third, fourth, and fifth postoperative days in group S compared with group C (p = 0.001, 0.001, and 0.001, respectively). The serum level of interleukin 6 showed a significant reduction on the fifth postoperative day in group S compared with group C (p = 0.001). There was no significant difference between the 2 groups regarding the troponin I level and inotropic score. Prophylactic use of high dose atorvastatin can decrease the incidence of POAF and attenuate the inflammatory process in adult patients undergoing isolated rheumatic cardiac valve replacement surgery.