This study examined the relationship between on-call duty exposure (active and total on-call hours a month, number of calls per duty) and employees’ experiences of being on-call (stress due to unpredictability, ability to relax during inactive on-call periods, restrictions during on-call duties, on-call work demands, and satisfaction with compensation for on-call duties) on the one hand and fatigue, strain-based and time-based work-home interference (WHI), and perceived on-call performance difficulties (PPD) on the other hand. Methods. Cross-sectional survey data were collected among a large heterogeneous sample of Dutch employees (N=5437). The final sample consisted of 157 on-call workers (23–69 years, 71% males). Data were analyzed by means of hierarchical regression analyses (controlling for age and job characteristics). Results. Differences in on-call work exposure were not systematically related to fatigue, WHI, and PPD (all p’s 0.50). The experience of being on-call explained a medium proportion of the variation in fatigue and strain-based WHI and a medium to large proportion of the variation in time-based WHI and PPD over and above the control variables. Conclusions. Our results suggest that it is employees’ experience of being on-call, especially the experience of stress due to the unpredictability, rather than the amount of exposure, that is related to fatigue, WHI, and perceived on-call performance difficulties.