ABSTRACT Background Amino acid imbalance, characterised by decreased branched‐chain amino acids (BCAAs) and increased tyrosine levels, is a common metabolic disturbance associated with various complications in patients with cirrhosis. However, the independent prognostic value of these changes remains unclear. Aims This study aimed to elucidate the prognostic impact of amino acid imbalance by analysing BCAA and tyrosine levels in patients with cirrhosis. Methods This multicenter retrospective study reviewed patients hospitalised for cirrhosis in Gifu, Japan. Amino acid imbalance was evaluated using serum BCAA and tyrosine levels and the BCAA‐to‐tyrosine ratio (BTR). Prognosis was assessed using a Cox proportional hazards regression model. Multivariable analyses were conducted using a model that included BTR, which was then replaced with both BCAA and tyrosine levels. Results Amongst 541 patients (median age, 66 years; 50.3% female), 129 (23.8%) died during a median follow‐up of 3.5 years. The median BTR, serum BCAA and tyrosine levels were 4.36, 378 and 90 μmol/L, respectively. Multivariable analysis identified BTR (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.72–0.94; p = 0.004) as a significant prognostic factor after adjustment for established factors. In the subsequent model, both BCAA (HR, 1.00; 95% CI, 1.00–1.00; p = 0.019) and tyrosine levels (HR, 1.01; 95% CI, 1.00–1.01; p = 0.002) independently predicted mortality. Conclusions Amino acid imbalance is an independent factor for poor prognosis in patients with cirrhosis. Notably, decreased BCAA and increased tyrosine levels were identified as independent prognostic factors.