Objective: To investigate the interaction between catechol-O-methyltransferase gene (COMT) Val108/158Met (rs4680) and season of birth (SOB) on ADHD and its symptoms. Method: We conducted transmission disequilibrium tests (TDTs) in 976 trios, then further performed the above analyses in subgroups according to SOB. Quantitative analyses were performed for ADHD symptoms evaluated by ADHD Rating Scale–IV in 1,530 ADHD cases. Results: Overall, there was no association between COMT and ADHD. After stratification, we found an increased transmission of the Val allele in the trios born in spring, while a decreased transmission was observed in the autumn months. We also observed a significant interaction between Val108/158Met and SOB on ADHD symptoms. Among those born in spring, Met carriers had milder ADHD symptoms compared with Val homozygotes, whereas opposite association was found in those born in autumn. Conclusion: Our study provided evidence for the modifying effect of SOB on the association between COMT and ADHD along with its symptoms.