To determine the causes of conjunctivitis and whether clinical presentations and outcomes differ by pathogen. This multicenter, case-control study enrolled 390 children (194 cases, 196 controls) whose conjunctival samples were tested for bacterial and viral pathogens. Caregivers completed surveys tracking symptoms, antibiotic use, school attendance, and adverse events. The outcomes analyzed included the prevalence of microorganisms detected by PCR in cases versus controls, symptoms, rate of resolution by day 5, school/childcare attendance, and parent-reported antibiotic-related adverse incidents. Most cases (148, 76%) and controls (112, 57%) had bacteria identified, although only detection of Haemophilus influenzae was associated with conjunctivitis (aOR 4.59, 95% CI 2.86, 7.37). Purulent discharge was associated with H. influenzae (aOR 2.47, 95% CI 1.23, 5.01) and occurred in 92 (77%) cases in which H. influenzae was detected and 39 (53%) in which H. influenzae was not detected. Improvement (186, 96%) and resolution (166, 86%) were observed by day 5 for most children and did not differ based on ophthalmic antibiotic use. Caregivers reported antibiotic-associated adverse events for 21 (20%) children with 8 (8%) requiring a medical visit. Only H. influenzae was significantly associated with conjunctivitis. Symptoms did not differ in children with or without bacteria detected by PCR. Independent of antibiotic use, most children experienced resolution by day 5, but parents reported adverse events in 20% of children treated with topical antibiotics, underscoring the importance of judicious prescribing.