Non-melanoma skin cancer (NMSC) is the most common cancer in the US, and having multiple lesions conveys substantial cost and morbidity for the individual involved. Although there are data available on risk factors for NMSC, there are currently few studies that identify specific risk factors for development of multiple NMSCs. We evaluated host risk factors for multiple NMSCs among men (Health Professionals Follow-up Study) and women (Nurses’ Health Study). Compared with individuals with a single NMSC, having greater number of sunburns was a risk factor for developing ≥2 NMSCs [≥10 sunburns, cumulative relative risk (RR) = 1.21, 95% confidence interval (CI): 1.07–1.36] and a higher risk of developing ≥11 NMSCs (≥10 sunburns, RR = 2.33, 95% CI: 1.57–3.46). Inability-to-tan was associated with risk of developing ≥2 NMSCs (cumulative RR = 1.29, 95% CI: 1.18–1.40) and a higher risk of developing ≥11 NMSCs (RR = 1.91, 95% CI: 1.50–2.43). Men had an increased risk of developing ≥2 NMSCs (cumulative RR = 1.53, 95% CI: 1.40–1.66). Risk of developing 2–4, 5–10 and ≥11 NMSCs increased with age. Other risk factors for developing ≥2 NMSCs included red natural hair colour (cumulative RR = 1.23, 95% CI: 1.07–1.42), family history of melanoma (cumulative RR = 1.15, 95% CI: 1.03–1.28), and having ≥6 nevi on the left arm (cumulative RR = 1.22, 95% CI: 1.07–1.40). In conclusion, physicians caring for individuals with incident NMSCs may consider paying special attention to those at highest risk for developing additional tumours, especially males and those with a history of ≥10 lifetime sunburns, by performing routine full skin examinations and counselling for aggressive photoprotection.