PURPOSE: Perioperative lignocaine enhances gastrointestinal recovery following colorectal surgery and may improve cancer outcomes via immune mediation of natural killer (NK) cells. This study aimed to assess the effect of lignocaine on immune function following laparoscopic colectomy. METHODOLOGY: A double blinded randomised placebo controlled clinical trial was conducted on patients undergoing elective laparoscopic resection for colorectal neoplasia. Perioperative intravenous and post-operative abdominal wall block lignocaine infusion were compared to placebo. The primary outcome was post-operative NK cell numbers and function. Secondary outcomes included cortisol, IL-2, IL-6, interferon gamma (IFN-γ), CRP, plasma lignocaine, length of stay (LOS), opiate consumption, return of gut function, surgical complications and mortality. RESULTS: Ninety-five patients were randomised to placebo (47) or lignocaine (48). Increased NK cell cytotoxic function from baseline was seen only in the lignocaine group, while the lignocaine group had higher numbers than placebo throughout the study period (p=0.016). There were supratherapeutic levels of plasma lignocaine after 24 hours (mean 5.71 mcg/ml). Differences were seen between groups in IL-2 levels at 72 hours (4.56; p=0.046), IL-6 at recovery entry (18.8; p=0.021) and IFN-γ at 1 hour (-6.99; p=0.029). There was no mortality in either group and no difference with respect to LOS (5 v 6 days; p=0.529). CONCLUSION: Perioperative lignocaine increases NK cell numbers, IL-6 and Il-2 activity and decreases IFN-γ levels post-operatively. High lignocaine levels were seen with abdominal wall infusion. Analgesic consumption was associated with serum lignocaine levels but not with the intervention.