Abstract Background: Diagnostic irradiation of the mother during pregnancy increases the risk of childhood acute lymphoblastic leukemia (ALL). There is inconsistent evidence on associations between ALL and other parental or childhood diagnostic irradiation. The aim of this analysis is to investigate whether diagnostic X-rays of the mother before birth, of the father before conception, or of the child increased the risk of childhood ALL. Methods: Data from 389 cases and 876 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching factors and potential confounders. A meta-analysis of our findings in relation to paternal X-rays before conception with the published findings of previous studies was also conducted. Results: There was no evidence of an increased risk with maternal abdominal X-rays before the birth of the index child or with the child having any X-rays more than 6 months before the censoring date. The odds ratio (OR) for any paternal abdominal X-ray before conception was 1.17 [95% confidence interval (95% CI), 0.88-1.55], and 1.47 (95% CI, 0.98-2.21) for more than one X-ray. The OR for any paternal intravenous pyelogram before conception was 3.56 (95% CI, 1.59-7.98). The pooled OR for this study with previous studies of any paternal abdominal X-rays before conception was 1.17 (95% CI, 0.92-1.48). Conclusions: There was some evidence of an increased risk of ALL in the offspring if the father had more than one abdominal X-ray before conception or had ever had an intravenous pyelogram. Impact: We plan to repeat this analysis by using pooled data to improve precision. Cancer Epidemiol Biomarkers Prev; 19(11); 2897–909. ©2010 AACR.