OBJECTIVES Many studies have been carried out to investigate the individual effects of vitamin C, vitamin E, and ibuprofen on flap viability, with favorable results. This study aimed to determine the effect of combined use of these agents on flap viability. DESIGN AND METHODS Sixty Wistar rats weighing 250-300 grams were divided into six groups, equal in number, to receive saline solution (group 1, control), vitamin C (group 2), vitamin E (group 3), vitamin C and E (group 4), ibuprofen (group 5), and vitamin C, vitamin E, and ibuprofen (group 6). Following ketamine anesthesia, a caudally based reverse McFarlane flap on the back of the rats, 3x10 cm in size, was elevated and sutured back. The agents were administered intraperitoneally once daily for seven days, after which viable flap areas were estimated. RESULTS The percentages of the viable area of the flaps in groups 1, 2, 3, 4, 5, and 6 were 58.0%, 68.1%, 61.4%, 73.4%, 69.1%, and 80.5%, respectively. The use of vitamin C, vitamin E, and ibuprofen in combination resulted in a significantly greater flap viability compared to individual uses. CONCLUSION Administering vitamin E and vitamin C together has a greater effect on flap viability than used alone; however, the benefit is the greatest with the addition of ibuprofen.