BACKGROUND: Surgical Site Infection (SSI) occurs in 9 % of laparoscopic colorectal surgery. Warming and humidifying carbon dioxide (CO2) used for peritoneal insufflation may protect against SSI by avoiding postoperative hypothermia (itself a risk factor for SSI). This study aimed to assess the impact of CO2 conditioning on postoperative hypothermia and SSI and to perform a cost-effectiveness analysis. METHODS: A retrospective cohort study of patients undergoing elective laparoscopic colorectal resection was performed at a single UK specialist centre. The control group (n = 123) received peritoneal insufflation with room temperature, dry CO2, whereas the intervention group (n = 123) received warm, humidified CO2 (using HumiGard™, Fisher & Paykel Healthcare). The outcomes were postoperative hypothermia, SSI and costs. Multivariate analysis was performed. RESULTS: A total of 246 patients were included in the study. The mean age was 68 (20-87) and mean BMI 28 (15-51). The primary diagnosis was cancer (n = 173), and there were no baseline differences between the groups. CO2 conditioning significantly decreased the incidence of postoperative hypothermia (odds ratio 0.10, 95 % CI 0.04-0.23), with hypothermic patients found to be at increased risk of SSI (odds ratio 4.0, 95 % CI 1.25-12.9). Use of conditioned CO2 significantly decreased the incidence of SSI by 66 % (p = 0.04). The intervention group incurred costs of £155 less per patient. The incremental cost-effectiveness ratio was negative. CONCLUSION: CO2 conditioning during laparoscopic colorectal surgery is a safe, feasible and a cost-effective intervention. It improves the quality of surgical care relating to SSI and postoperative hypothermia.