Aim: This study systematically reviewed the relationship between plasma drug concentrations of perioperative intravenous lignocaine and its analgesic effects. Methods: Randomised controlled trials of adults undergoing non-cardiac surgeries were systematically searched and reviewed in SCOPUS, Medline, EMBASE, CENTRAL, and Web of Science from inception to March 2024. These trials compared lignocaine to placebo or control, assessed pain outcomes, administered lignocaine intraoperatively, and reported plasma lignocaine concentrations at various time points. Outcomes included cumulative opioid use (measured in IV morphine equivalent), pain scores, and hospital stay duration. The Cochrane risk-of-bias tool was used for bias assessment, and data were analysed with a random-effects model to determine the mean difference (MD) and 95% confidence intervals (CI). The review protocol was registered at INPLASY (INPLASY202180046). Results: Fifteen studies with 445 lignocaine and 453 control patients were included. Eight studies showed lower opioid use in the post-anaesthetic care unit (PACU) for the lignocaine group (MD of -3.00 (95% CI [-5.00, -1.01], P=0.0092, I2=57%). Meta-regression indicated higher plasma concentrations of lignocaine correlated with greater opioid reduction (regression coefficient of -3.05 [95% CI -4.48, -1.61], P=0.002). However, eleven studies found no significant difference in opioid consumption and pain scores at 24 hours post-surgery. Incidence of nausea and vomiting was similar between the groups, and few patients had lignocaine-related adverse reactions. Conclusions: Perioperative lignocaine infusion effectively reduces opioid consumption in the PACU, with more pronounced effects at higher plasma concentrations. Further research is needed to identify optimal plasma concentrations for clinically significant analgesic benefits.