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Background Adult literature has demonstrated chlorhexidine (CH) superiority at preventing surgical-site infections when compared with povidone-iodine (P-I). The purpose of this study is to compare the rate of postoperative infections after preoperative skin cleansing with either CH or P-I in pediatric orthopaedic surgery in an effort to identify superiority. Methods We retrospectively identified all patients (18 y and below) that underwent orthopaedic surgery at our institution in 2015, when P-I was the preoperative skin antisepsis of choice, and in 2018, when a change in protocol resulted in more frequent use of CH. Open fractures, infections, neuromuscular, and tumor surgeries were excluded. Orthopaedic surgeries were classified according to their subspecialty (sports-related/upper extremity, hip and lower extremity, trauma-related, or spine procedure). A 1:1 propensity score matching was conducted within each procedure group on the basis of age, sex, and year using nearest-neighbor matching. Spine procedures could not be matched and were subsequently excluded from analyses. Results Propensity score matching matched 1416 CH cases with 1416 P-I controls. The infection rate for CH was 19 infections per 1000 cases (27/1416; 1.9%) compared with an infection rate of 11 infections per 1000 cases (16/1416; 1.1%) for P-I subjects. No difference was detected in infection rate across preoperative skin antisepsis groups (P=0.12). Moreover, it was found that CH and P-I resulted in significantly equivalent infection rates to within ±1.5% (P=0.004). When stratified by procedure type, CH used in sports/upper extremity procedures resulted in 29 more infections per 1000 cases compared with P-I use (16/450; 3/450; P=0.005). No difference was detected in infection rate across CH and P-I skin antisepsis groups in lower extremity procedures (9/792; 8/792; P=1.00) or in trauma-related procedures (3/174; 4/174; P=1.00). Conclusions CH and P-I are both protective against postoperative infections after sports/upper extremity, lower extremity, and trauma-related pediatric orthopaedic procedures. P-I may provide improved protection over CH as a preoperative skin antisepsis in upper extremity and sports-related procedures. Level of evidence Level III-comparative cohort.