Purpose Symptoms of urinary irritation, urgency, frequency, and obstruction, known as lower urinary tract symptoms (LUTS), are common in urological practice. However, little is known about the etiology or pathogenesis of LUTS, especially the relative contributions of genetic and environmental factors to development of these symptoms. We used a classical twin study design to examine the relative contribution of genetic and environmental factors to the occurrence of LUTS in middle-aged men. Materials and Methods Twins were members of the Vietnam Era Twin (VET) Registry. We used a mail survey to collect lower urinary tract symptoms (LUTS) using the International Prostate Symptom Score (I-PSS) instrument. Twin correlations and biometric modeling was used to determine the relative genetic and environmental contributions to variance in I-PSS total score and individual items. Results Participants were 1,002 monozygotic and 580 dizygotic middle-aged male twin pairs (mean age = 50.2 years; S.D. = 3.0 years). Nearly 25% of the sample had an I-PSS score > 8, indicating at least moderate LUTS. The heritability of the total I-PSS was 37% (95% CI = 32-42%). Heritability estimates ranged from 21% for nocturia to 40% for straining, with moderate heritability (34–36%) for urinary frequency and urgency. Conclusions Genetic factors provide a moderate contribution (20–40%) to LUTS in middle-aged men, suggesting that environmental factors may also contribute substantially to LUTS. Future research is needed to define specific genetic and environmental mechanisms that underlie the development of these symptoms and conditions associated with LUTS.