Purpose To test for association between single nucleotide polymorphisms at the TGFβ1 locus and the risk of late normal tissue injury following whole breast radiotherapy. Methods A retrospective study compared the number of variant alleles at −509 and codons 10 and 25 of the TGFβ1 locus in women followed up in two prospective clinical trials who developed either marked radiotherapy adverse effects or no adverse effects after matching on fractionation schedule, breast size, surgical deficit, chemotherapy and length of follow up. Results Median follow up in the two trials was 7.4 (maximum 15) years and 5.3 (maximum 5.3) years. 1237/1716 (72%) women with photographic assessments of radiotherapy adverse effects were alive and well, and 147/1237 (12%) potential cases with the most marked change in photographic change in breast appearance were matched to potential controls recording no change. In an unmatched analysis of 82 cases and 108 controls, no significant difference in the number of genetic variants was observed. Conclusions No association was detected between sequence variations at the TGFβ1 locus and the risk of late adverse effects of breast radiotherapy.