We investigated the relationship between shift work and excessive daytime sleepiness (EDS) among participants in the Japan Nurses’ Health Study (JNHS). Responses of 9,728 female nurses to the 6th follow-up questionnaire were cross-sectionally analyzed. EDS was defined as an Epworth Sleepiness Scale score ≥11. EDS-associated factors were evaluated using Poisson regression analysis after adjustment for multiple confounders. Of the participants (mean age, 52.2 ± 8.0 yr), 28.7% were engaged in shift work, and the overall prevalence of EDS was 24.6%. EDS-associated factors were investigated separately in women aged <40 yr (n=250), 40-59 yr (n=7,467), and ≥60 yr (n=2,011). Current engagement in shift work (prevalence ratio: 1.92 [95% confidence interval: 1.20-3.06], compared with no experience of shift work) and obesity (2.08 [1.11-3.88] for BMI ≥30 and 1.39 [1.02-1.90] for BMI of 25.0-30.0, compared with BMI of 18.5-25.0) showed an independent association with EDS in women aged ≥60 yr. The effect of shift work on EDS in female nurses differed by age, as shift work and obesity contributed to EDS only in older participants. Shift work should be assigned after full consideration of age, sleep, and health status to minimize medical errors.