Single nucleotide polymorphisms (SNPs) of collagen genes have been associated with soft-tissue injury and running performance. However, their combined contribution to running performance is unknown. We investigated the association of two collagen gene SNPs with athlete status and performance in 1429 Caucasian participants, including 597 competitive runners (354 men, 243 women) and 832 non-athletes (490 men, 342 women). Genotyping for COL1A1 rs1800012 (C>A) and COL5A1 rs12722 (C>T) SNPs was performed by real-time polymerase chain reaction. The numbers of ‘injury-resistant’ alleles from each SNP, based on previous literature (rs1800012 A allele, rs12722 C allele), were combined as an injury-resistance score (RScore, 0 to 4; higher scores indicate injury-resistance). Genotype frequencies, individually and combined as RScore, were compared between cohorts and investigated for associations with performance via official race times. Runners had 1.34 times greater odds of being rs12722 CC homozygotes than non-athletes (19.7% vs. 15.5%, P=0.020) with no difference in rs1800012 genotype distribution (P=0.659). Fewer runners had RScore 0 (18.5% vs. 24.7%) and more had RScore 4 (0.6% vs. 0.3%) than non-athletes (P<0.001). Competitive performance was not associated with COL1A1 genotype (P=0.933), COL5A1 genotype (P=0.613) or RScore (P=0.477). Whilst not associated directly with running performance amongst competitive runners, a higher combined frequency of injury-resistant COL1A1 rs1800012 A and COL5A1 rs12722 C alleles in competitive runners than non-athletes suggests these SNPs may be advantageous via a mechanism that supports, but does not directly enhance, running performance.