We investigated the difference in sleep inertia between shift workers (SWs) and non-shift workers (NSWs) and the effects of depressive symptoms, sleepiness, insomnia, and chronotype on sleep inertia in SWs and NSWs. Altogether, 4,561 SWs (2,142 men and 2,419 women, aged 36.99±9.84 years) and 2,093 NSWs (999 men and 1,094 women, aged 37.80±9.73 years) participated in the current study. All participants completed the Sleep Inertia Questionnaire (SIQ), Epidemiological Studies Depression Scale (CESD), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and Morningness-Eveningness Questionnaire (MEQ) through an online survey. SWs reported higher SIQ scores than NSWs after controlling for CESD, ESS, ISI, or MEQ. The CESD, ESS, ISI, and MEQ predicted SIQ in both SWs and NSWs. The effects of CESD and MEQ on SIQ were stronger in SWs and NSWs, respectively. The indirect effects of CESD and MEQ on SIQ via ESS were significantly moderated by work schedules. SWs showed higher sleep inertia than NSWs. The effect of chronotypes on sleep inertia was more prominent in NSWs than in SWs. However, the effect of depressive symptoms on sleep inertia was more prominent in SWs than in NSWs. Moreover, the effect of depressive symptoms or chronotypes on sleep inertia was mediated by sleepiness, and such indirect effects were significantly different among the participants stratified by work schedules.