Objective: To compare the frequency of postoperative surgical site infection (SSI) by type of skin preparation used for unscheduled cesarean in the setting of adjunctive azithromycin prophylaxis. Methods: Secondary analysis of a multi-center randomized controlled trial of adjunctive azithromycin (500 mg intravenous) versus placebo in women who were ≥24 weeks gestation and undergoing unscheduled cesarean (i.e. during labor or ≥4 h after membrane rupture). Type of skin preparation used was identified based on the protocol at the hospital at the time of delivery: iodine-alcohol, chlorhexidine, chlorhexidine-alcohol, or the combination of chlorhexidine-alcohol and iodine. The primary outcome of this analysis was incidence of post-operative SSI, as defined by CDC criteria. Multivariable logistic regression was applied for adjustments. Results: All 2013 women in the primary trial were included in this analysis. Women were grouped according to type of skin preparation received: iodine-alcohol (n = 193), chlorhexidine (n = 733), chlorhexidine-alcohol (n = 656), and chlorhexidine-alcohol and iodine combined sequentially (n = 431). The unadjusted rates of wound infection ranged from 2.9% to 5.7%. Using iodine-alcohol as the referent, the adjusted odds ratios for wound SSI were 0.71 (95% CI 0.30–1.66) for chlorhexidine, 0.97 (95% CI 0.41–2.28) for chlorhexidine-alcohol, and 0.88 (95% CI 0.36–2.20) for chlorhexidine-alcohol with iodine combination. Conclusion: In women undergoing unscheduled cesarean delivery in a trial of adjunctive azithromycin, the type of skin preparation used did not appear to be associated with the frequency of wound SSI.