X-ray screening of passenger baggage is a key component in aviation security. The current study investigated how experts and novices performed in an X-ray baggage screening task while being assisted by an adaptable diagnostic aid. Furthermore, it examined how both groups operated and trusted this automated system. 30 experts (certified screeners) and 31 novices (students) had to indicate whether a target item (either a knife or a gun) was present in a series of X-ray images of cabin baggage. Half of the participants could choose between three different support levels of the diagnostic aid (DA): (1) no support, (2) a cue indicating the presence of a potential target without locating it, or (3) a cue indicating the presence of a potential target by surrounding it with a red frame. As expected, experts achieved higher detection performance (d’), were more self-confident and felt more competent in achieving the task than novices. Furthermore, experts experienced less time pressure and fatigue. Although both groups used the DA in a comparable way (in terms of support level used and frequency of level switches), results showed a performance increase for novices working with the DA compared to novices without support. This benefit of DA was not observed for experts. Interestingly, despite no difference in perceived trust ratings, experts were more compliant (i.e., following DA recommendations when it indicated the presence of a target) and reliant (i.e., following DA recommendations when it indicated the absence of a target) than novices. Altogether, the results of the present study suggested that novices benefited more from a DA than experts. Furthermore, compliance and reliance on DA seemed to depend on expertise with the task. Since experts should be better at assessing the reliability of the DA than novices, they may have used the DA as ‘back-up’ to confirm their decisions based on expertise (confirmatory function), while novices may have used it as a guide to base their decisions on (support function). Finally, trust towards a DA was associated with the degree to which participants found the DA useful.