Introduction <p>Congenital dacryocystocele (CD) represents a rare yet clinically significant subtype of congenital nasolacrimal duct obstruction. It carries a substantial risk of severe secondary infection, yet its risk factors have not been fully elucidated. This study aimed to identify the independent risk factors for secondary infection in infants with CD and to evaluate the impact of infection on treatment course and prognosis.</p> Methods <p>A retrospective cohort study was conducted in 100 infants (118 eyes) diagnosed and treated for CD in a tertiary hospital between January 2017 and December 2024. Demographic characteristics, clinical features, and treatment details were collected and analyzed. Univariate analysis and a multivariate logistic regression model were used to identify independent risk factors associated with secondary infection.</p> Results <p>Secondary infection occurred in 60 of the 118 eyes (50.85%, 95% confidence interval (CI): 41.50–60.20%). Multivariate logistic regression analysis identified three independent risk factors for secondary infection: concomitant intranasal cyst (adjusted odds ratio (aOR) = 5.07, 95% CI: 2.10–12.23, <i>p</i> &lt; 0.001), a history of lacrimal sac massage (aOR = 3.11, 95% CI: 1.29–7.46, <i>p</i> = 0.01), and disease onset during the winter–spring season (aOR = 2.97, 95% CI: 1.27–6.93, <i>p</i> = 0.01). Compared to the non-infected group, infants with secondary infection required a significantly longer treatment duration (median: 6.00&#xa0;days vs.1.00&#xa0;day, <i>p</i> &lt; 0.001) and required more invasive management.</p> Conclusions <p>Concomitant intranasal cyst, a history of lacrimal sac massage, and winter–spring season onset are strong independent predictors of secondary infection in CD. Secondary infection is associated with not only a prolonged treatment course but also a higher probability of invasive intervention. These findings highlight the need for accurate diagnosis and adherence to standardized treatment protocols in infants with CD.</p>