Hyperammonemia is an important stimulator of myostatin expression, a negative regulator of muscle growth. After splenectomy or partial splenic artery embolization (PSE), hyperammonemia often improves. Thus, we investigated changes in skeletal muscle index (SMI) in patients following an operation on the spleen and in patients who did not undergo an operation on their spleen. The study was designed retrospectively, in which we analyzed data collected between January 2000 and December 2015. Patients were assigned to the splenectomy/PSE or nontreatment group. Changes in SMI (ΔSMI), ammonia (Δammonia), myostatin (Δmyostatin), irisin (Δirisin), and branched‐chain amino acids/tyrosine molar ratio (ΔBTR) were analyzed between baseline and 5‐year follow‐up both before and after inverse probability of treatment weighting adjustment (IPTW). Patients (102) were enrolled (splenectomy/PSE, n = 45; nontreatment group, n = 57) before IPTW adjustment: ΔSMI (2.6 cm2/m2 vs. −8.8 cm2/m2, respectively) (P < 0.001), Δmyostatin (−867 vs. −568, respectively) (P < 0.001), Δammonia (−34 and 16, respectively) (P < 0.001), and ΔBTR (0.89 and −0.665, respectively) (P < 0.001). There were no differences between splenectomy and PSE regarding these factors. Moreover, after IPTW adjustment, significant differences were observed between the splenectomy/PSE and nontreatment group for the median ΔBTR (0.89 and −0.64, respectively) (P < 0.001), Δammonia (−33 and 16, respectively) (P < 0.001), Δmyostatin (−894 and 504, respectively) (P < 0.001), and ΔSMI (1.8 cm2/m2 and −8.2 cm2/m2, respectively) (P < 0.001). Conclusions: Both splenectomy and PSE were associated with the prevention of secondary sarcopenia in patients with LC. Moreover, it can be expected that muscle volume loss is reduced by splenectomy or PSE in patients with hyperammonemia.