Objective <p>Lower respiratory tract infections (LRTIs) are a common cause of primary care visits in infants. This study was done to evaluate the course of LRTIs before-and-after the introduction of nirsevimab and to identify the associated risk factors.</p> Methods <p>This was a quasi-experimental, before-and-after study, comparing two cohorts of infants followed during their first year of life, before (April–December 2017–2018) and after (April–December 2023–2024) following the introduction of nirsevimab. Clinical, epidemiological, and healthcare-related variables were analyzed.</p> Results <p>A total of 729 infants were included (<i>n</i> = 327 in 2017–2018; <i>n</i> = 402 in 2023–2024); 91.0% of infants in the second period received nirsevimab. The overall incidence of LRTIs did not differ between the two periods (26.3% vs. 23.9%; <i>P</i> = 0.453). Following the introduction of nirsevimab, diagnoses and follow-up in primary care increased (+ 35.3% and + 28.4%, respectively; both <i>P</i> &lt; 0.001). No differences were observed in clinical severity (<i>P</i> = 0.301), emergency department referrals (<i>P</i> = 1.000), pharmacological treatment (<i>P</i> = 0.791), recurrences (<i>P</i> = 0.110), or hospitalizations (<i>P</i> = 1.000). In multivariable analysis, LRTI occurrence was independently associated with male sex, daycare attendance, school-aged siblings, passive smoking exposure, and lack of nirsevimab immunoprophylaxis.</p> Conclusions <p>The introduction of nirsevimab did not affect the severity of LRTI and was accompanied by a greater proportion of cases managed in primary care.</p>