Background <p>Infants are the most frequently hospitalized group for respiratory tract infections, and rapid and accurate pathogen identification is critical for effective management. However, conventional diagnostic methods often have limited sensitivity and a narrow detection range. This study aimed to compare the detection of respiratory pathogens in infants using targeted next-generation sequencing (tNGS) and conventional methods in Qingdao, China.</p> Methods <p>This study included infants aged 0–1 year with a respiratory infection (i.e., presenting with at least two of the following: cough, nasal congestion, sputum, sneezing, or dyspnea) admitted to Qingdao Women and Children’s Hospital from March to May 2023. Bacterial culture, isothermal amplification, fluorescent PCR, and tNGS were performed to detect common pathogens.</p> Results <p>The study included 95 patients. The highest positive rates were for the respiratory syncytial virus (RSV) (34/95, 35.8%), followed by influenza A virus (IAV) (17/95, 17.9%) and <i>Acinetobacter baumannii (A. baumannii)</i> (17/95, 17.9%). Single-pathogen infections accounted for 47.4%, and mixed infections for 47.4%. The positive detection rates for conventional methods and tNGS were 27.4% and 91.6%, respectively. The consistency rate between tNGS and conventional methods was 76.9%. There were significant differences between the two methods in the detection rates of viruses (<i>P</i> = 0.049) and bacteria (<i>P</i> = 0.016). The detection rate of pathogens using tNGS was higher than that with conventional methods (<i>P</i> = 0.023).</p> Conclusions <p>RSV, IAV, <i>A. baumannii</i>, HRV, and <i>S. pneumoniae</i> are common pathogens in infants &lt; 1 year old in Qingdao (China). tNGS is more sensitive and has a wider detection range than conventional methods.</p> Clinical trial number <p>Not applicable.</p>