Surgical site infection (SSI) can affect the quality of care and increase the morbidity and mortality rate in after-surgical procedure. The use of an antiseptic skin preparation agent before the procedure can reduce the pathogens in the skin surface around the incision. Indicating the type of skin antiseptic preparation could prevent the infection and contamination of the wound. The most commonly used types of skin preparations are chlorhexidine and povidone iodine. However, the antiseptic solutions of both agents are strengthened with alcohol to prevent postoperative wound infection. The aim of this paper is to identify the best antiseptic agent in terms of skin preparation by evaluating the evidence in the literature. The factors associated with choosing the antiseptic skin agent, such as patients' allergies, skin condition and environmental risk, are also taken into account. This review suggests that cholorhexdine with alcohol may be the most effective in terms of reducing SSI.