Purpose: To assess the perinatal risk factors, clinical characteristics, and microbial profile in congenital nasolacrimal duct obstruction (CNLDO). Methods: A prospective observational study was conducted in pediatric patients of age <5 years. After a thorough clinical evaluation, the diagnosis of the CNLDO was confirmed by a Jones dye test or fluorescein dye disappearance test. A microbiological culture of lacrimal sac resurge was done with a sterile swab stick without touching the lid margins. Antibiotic susceptibility was then performed for the standard antibiotics. Results: Seventy-one eyes of 52 children were included in the study. The mean age was 3.4 months. Our research found an equal number of cases born via spontaneous vaginal delivery and Caesarean section. Nine children (17.3%) had associated systemic and ocular anomalies. The number of cultures that were positive for any growth was 19 (27%). The most common isolate was Streptococcus pneumoniae which constituted eight cases (42%), followed by Pseudomonas aeruginosa (15.8%), and Escherichia coli (10.5%). Other organisms that grew were Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis and nonfermenting gram-negative bacilli. Gram-positive organisms were susceptible to ciprofloxacin, amoxiclav, and oxacillin, and most of them were resistant to erythromycin. In comparison, gram-negative organisms showed 62.5% resistance and 37.5% susceptibility to ciprofloxacin. Conclusions CNLDO was more commonly unilateral, in male, preterm, and normal birth weight infants. Bilateral CNLDO was more commonly associated with coexisting ocular or systemic anomalies. Prematurity, delivery by Caesarean section, and presence of congenital anomalies were associated with a prolonged course. S. pneumoniae was the predominant isolate in our patient population.