Objective: To investigate whether smoking, alcohol intake, female hormonal or anthropometric factors affect melanoma risk. Methods: Using Cox proportional hazards regression analyses, we analyzed 68,588 white subjects (79% female) from the US Radiologic Technologists (USRT) Study who were cancer-free (other than non-melanoma skin cancer) as of the first of two self-administered questionnaires. Follow-up covered 698,028 person-years, with 207 cases of melanoma. Results: We found that melanoma risk was not associated with height, weight or BMI, nor with age at menarche, menopausal status, use of hormone replacement therapy, parity, age at first birth or oral contraceptive use. Melanoma risk was elevated with increasing alcohol use (RR: 2.1; 95% CI: 0.9–4.8, for >14 drinks/week compared to never drinking; (p(trend) = 0.08)). Smoking for long durations compared to never smoking was inversely related to melanoma risk (RR: 0.6; 0.3–1.3; ≥30 years; p(trend) = 0.03), though risk was not associated with number of packs smoked per day. Conclusions: None of the anthropometric or female reproductive/hormonal factors evaluated were related to melanoma risk. It is unclear whether the positive association with alcohol intake and inverse association with smoking for long duration are causal. The alcohol and smoking findings warrant detailed assessment in studies with substantial statistical power where potential biases can be more fully evaluated.