Background: Isoflurane and propofol are routinely used for the maintenance of general anaesthesia. However, recently, they have been implicated in hepatotoxicity resulting in acute liver failure. Objective: We compared the effects of isoflurane and propofol on liver enzymes; aspartate transaminases (AST), alanine transaminases (ALT), alkaline phosphatase (ALP) and total bilirubin (Tbil) following general anaesthesia. Materials and Methods: This randomized, controlled clinical trial involved 60 ASA I and II patients aged 18–64 years scheduled for elective surgery requiring general anaesthesia. Anaesthesia was induced with intravenous sodium thiopentone 5 mg/kg and atracurium 0.5 mg/kg, and maintained in group I with isoflurane (MAC, 0.8%-1.5%) and in group P with (propofol infusion, 100–200µg/kg/minute). Blood samples were taken pre-induction, immediate- and 24 hours post operatively. The serum levels of AST, ALT, ALP, Tbil were analyzed and compared in both groups. Risk factors for post operative hepatotoxicity were determined. Result: Propofol caused a significant reduction in ALP ( P = 0.005) but increase in Tbil ( P = 0.010) 24 hours postoperatively. Though isoflurane had consistently higher values of AST, ALP and Tbil than propofol, only the mean AST values at 24 hours post-operative was significantly higher ( P = 0.045). There was a significant increase in the 24 hours post-operative Tbil following massive blood loss; [odd ratio 23.91, 95%, CI (1.685–339.315)], P = 0.019. Conclusion: Both agents had a varied effect on liver enzymes. Isoflurane resulted in a significantly higher increase in 24 hours post-operative serum AST than propofol. Propofol caused a significant increase in 24 hours post-operative total bilirubin. Caution is therefore recommended in their use in patients with altered liver enzymes.