© 2016 Prahalad et al. Background: Clinically distinct autoimmune phenotypes share genetic susceptibility factors. We investigated the prevalence of familial autoimmunity among subjects with juvenile idiopathic arthritis (JIA), childhood systemic lupus erythematosus (cSLE) and juvenile dermatomyositis (JDM) in the CARRA Registry, the largest multicenter observational Registry for pediatric rheumatic disease. Methods: Children with JIA, cSLE and JDM enrolled in the CARRA Registry between May 2010 and May 2012 were investigated for differences in proportion of subjects who had first-degree relatives (FDR) with autoimmunity. If a significant difference was detected, pairwise comparisons, adjusted for multiple comparisons, were made. Results: There were 4677 JIA, 639 cSLE and 440 JDM subjects. The proportion of subjects having FDR with any autoimmune disease in the JDM group (20.5%) was less compared to subjects with JIA (31.8%, p < 0.001) or SLE (31.9%; p < 0.001). Significantly greater proportion of JIA cases had FDR with inflammatory arthritis (13%) compared to cSLE (9.2%, p = 0.007) or JDM (4.3%, p <0.001). Significantly greater proportion of cSLE cases had FDR with SLE (11.1% vs. 1.7% for JIA and 1.1% for JDM p < 0.001) or type-I diabetes (7.4% for cSLE vs. 3.1% for JIA and 3.0% for JDM p < 0.001). Conclusion: Higher proportions of subjects with JIA and cSLE have FDR with autoimmunity compared to those of JDM. Relatives of cSLE cases had an increased prevalence of SLE, and relatives of JIA cases were enriched for inflammatory arthropathies demonstrating distinct patterns of familial autoimmunity among these phenotypes.