Amiodarone (AMD) is characterized by complex pharmacokinetics involving high lipophilicity and extensive protein binding. Serum AMD concentrations are influenced by triglyceride (TG) levels. Although the impact of TG on AMD concentrations at steady state has been previously investigated, data regarding the initial treatment period are limited. Given the prolonged half-life of AMD and the need for dose adjustments prior to reaching steady state, elucidating the effect of TG during this early phase is important. This retrospective study analyzed 64 patients who received AMD therapy at Sapporo City General Hospital between January 2016 and December 2024. Serum levels of AMD, its active metabolite desethylamiodarone (DEA), TG, and albumin were measured during the initial period (4–6 months) and steady-state period (7–12 months). Concentration-to-dose (C/D) ratios were calculated to assess pharmacokinetic variability during each period. Significant positive correlations were observed between serum TG levels and C/D_AMD during the initial (r=0.424, p<0.05) and steady-state (r=0.492, p<0.01) periods. A modest but significant correlation was observed between TG and C/D_DEA during the steady-state period (r=0.304, p<0.05). No significant correlations were found between albumin and C/D_AMD or C/D_DEA at any period. Serum TG levels affected AMD concentrations from the initial treatment period; however, the pharmacologically active unbound fraction remained stable. Consequently, dose adjustments based solely on fluctuations in TG levels are not required during the initial period. These findings contribute to the development of more precise AMD dosing strategies to maintain antiarrhythmic efficacy from treatment initiation.