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The emergence of SARS-CoV-2 and the implementation of non-pharmaceutical interventions (NPIs) profoundly disrupted the transmission dynamics of respiratory viruses, altering their epidemiology and seasonality. However, comprehensive long-term data on these shifts and their post-pandemic implications remain limited. This study analyzed syndromic multiplex panel testing data from 83'823 respiratory specimens collected from 56,519 patients with respiratory tract infections (RTIs) at two tertiary care centers in northwestern Switzerland to systematically assess changes in respiratory virus circulation, seasonality, age distribution, and disease burden across pre-pandemic (2010-2019), pandemic (2019-2022), and post-pandemic (2022-2024) periods. Pre-pandemic, influenza virus (IV), respiratory syncytial virus (RSV), human coronavirus (HCoV), human metapneumovirus (hMPV), and human parainfluenza virus (HPIV) followed distinct seasonal patterns. During the pandemic, SARS-CoV-2 replaced these viruses, leading to a 70-90% decline in their activity (p < 0.001), while rhinovirus/enterovirus and adenovirus were less affected. After NPIs were lifted, substantial off-season activity with markedly higher case numbers and more hospitalizations, especially among pediatric patients, occurred for IV-A/B, RSV, and atypical bacteria. In post pandemic years, virus-specific seasonality is rebounding, with patterns resembling those seen pre-pandemic. However, higher case numbers, increased hospitalizations, and sustained shifts in age distribution persist. The COVID-19 panemic significantly impacted the etiology, seasonality, and age distribution of RTIs. As NPIs were eased, susceptibility to RTIs, particularly among pediatric patients, increased, resulting in more hospitalizations. While post-pandemic periods show a return to pre-pandemic activity patterns, ongoing monitoring is essential to anticipate shifts in respiratory virus dynamics as immunity levels and virus characteristics evolve.