To determine whether neonatal phototherapy is associated with cancer in the first year after birth. We analyzed a data set from the California Office of Statewide Health Planning and Development that was created by linking birth certificates, death certificates, and hospital discharge abstracts up to age 1 year. Subjects were 5?144?849 infants born in California hospitals at ?35 weeks’ gestation from 1998 to 2007. We used International Classification of Diseases, Ninth Revision codes to identify phototherapy at <15 days and discharge diagnoses of cancer at 61 to 365 days. We adjusted for potential confounding variables by using traditional and propensity-adjusted logistic regression models. Cancer was diagnosed in 58/178?017 infants with diagnosis codes for phototherapy and 1042/4?966?832 infants without such codes (32.6/100?000 vs 21.0/100?000; relative risk 1.6; 95% confidence interval [CI], 1.2-2.0, P = .002). In propensity-adjusted analyses, associations were seen between phototherapy and overall cancer (adjusted odds ratio [aOR] 1.4; 95% CI, 1.1-1.9), myeloid leukemia (aOR 2.6; 95% CI, 1.3-5.0), and kidney cancer (aOR 2.5; 95% CI, 1.2-5.1). The marginal propensity-adjusted absolute risk increase for cancer after phototherapy in the total population was 9.4/100?000 (number needed to harm of 10?638). Because of the higher baseline risk of cancer in infants with Down syndrome, the number needed to harm was 1285. Phototherapy may slightly increase the risk of cancer in infancy, although the absolute risk increase is small. This risk should be considered when making phototherapy treatment decisions, especially for infants with bilirubin levels below current treatment guidelines.