Purpose To assess melanoma risk in relation to sunscreen use and to compare high- with low-sun protection factor (SPF) sunscreens in relation to sunbathing habits in a large cohort study. Materials and Methods We used data from the Norwegian Women and Cancer Study, a prospective population-based study of 143,844 women age 40 to 75 years at inclusion with 1,532,247 person-years of follow-up and 722 cases of melanoma. Multivariable Cox proportional hazards regression was used to estimate the association between sunscreen use (never, SPF < 15, SPF ≥ 15) and melanoma risk by calculating hazard ratios and 95% CIs. The population attributable fraction associated with sunscreen use was estimated. Results Sunscreen users reported significantly more sunburns and sunbathing vacations and were more likely to use indoor tanning devices. SPF ≥ 15 sunscreen use was associated with significantly decreased melanoma risk compared with SPF < 15 use (hazard ratio, 0.67; 95% CI, 0.53 to 0.83). The estimated decrease in melanoma (population attributable fraction) with general use of SPF ≥ 15 sunscreens by women age 40 to 75 years was 18% (95% CI, 4% to 30%). Conclusion Use of SPF ≥ 15 rather than SPF < 15 sunscreens reduces melanoma risk. Moreover, use of SPF ≥ 15 sunscreen by all women age 40 to 75 years could potentially reduce their melanoma incidence by 18%.