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To examine whether a mismatch between chronotype (i.e., preferred sleep timing) and work schedule is associated with type 2 diabetes risk.In the Nurses’ Health Study 2, we followed 64,615 women from 2005 to 2011. Newly developed type 2 diabetes was the outcome measure (n = 1,452). A question on diurnal preference ascertained chronotype in 2009; rotating night shift work exposure was assessed regularly since 1989.Compared with intermediate chronotypes, early chronotypes had a slightly decreased diabetes risk after multivariable adjustment (odds ratio 0.87 [95% CI 0.77–0.98]), whereas no significant association was observed for late chronotypes (1.04 [0.89–1.21]). Among early chronotypes, risk of type 2 diabetes was modestly reduced when working daytime schedules (0.81 [0.63–1.04]) and remained similarly reduced in women working <10 years of rotating night shifts (0.84 [0.72–0.98]). After ≥10 years of shift work exposure, early chronotypes had a nonsignificant elevated diabetes risk (1.15 [0.81–1.63], Ptrend = 0.014). By contrast, among late chronotypes, the significantly increased diabetes risk observed among day workers (1.51 [1.13–2.02]) appeared largely attenuated if their work schedules included night shifts (<10 years: 0.93 [0.76–1.13]; ≥10 years: 0.87 [0.56–1.34]; Ptrend = 0.14). The interaction between chronotype and shift work exposure was significant (Pinteraction = 0.0004). Analyses restricting to incident cases revealed similar patterns.In early chronotypes, type 2 diabetes risk increased with increasing duration of shift work exposure, whereas late types had the highest diabetes risk working daytime schedules. These data add to the growing body of evidence that workers could benefit from shift schedules minimizing interference with chronotype-dependent sleep timing.