BackgroundThe Trier Social Stress Test (TSST) is a widely used laboratory protocol to study acute stress reactivity, a hallmark of which is a meaningful increase in saliva cortisol (> 2.5 nmol/L) in most individuals, reflecting hypothalamic-pituitary-adrenal (HPA) axis activation. The Mannheim Multicomponent Stress Test (MMST) has potential as a low staff burden alternative to the TSST, with one study showing statistically significant increases in subjective stress, heart rate and saliva cortisol; however, uncertainty remains about the meaningfulness of these psychobiological responses. ObjectiveTo assess whether the MMST is a viable alternative to the TSST. MethodsUsing a between subjects design, 31 healthy adults were randomised to the standard TSST or the MMST using stratified block randomisation accounting for sex and trait anxiety. The standard TSST consisted of an anticipation phase, followed by a free speech and mental arithmetic task performed in front of a panel of trained actors. The MMST consisted of a computer based Paced Auditory Serial Addition Task (cognitive stressor) with additional motivational, emotional, and acoustic stressors in the presence of one unresponsive observer. ResultsGroup x time interactions showed that the MMST induced smaller psychobiological responses compared with the TSST (mixed model ANCOVA, P < 0.05). Post-hoc analyses revealed that the MMST induced a significant yet smaller state anxiety response (score range 20–80, MMST: 47 ± 12 vs. TSST: 57 ± 9; P < 0.01, Cohens d = 0.9) and peak heart rate response (MMST: 98 ± 17 vs. TSST: 110 ± 21 bpm; P < 0.05, Cohens d = 0.6) compared with the TSST. Despite observing stereotypical neuroendocrine responses to the TSST, the MMST did not increase saliva α-amylase or cortisol (Δ saliva cortisol, 0.1 ± 1.1 vs. TSST: 10.3 ± 12.8 nmol/L; between group difference P < 0.01, Cohens d = 1.1). Moreover, meaningful increases in saliva cortisol (> 2.5 nmol/L) were observed in 80% of participants after the TSST but in no participant after the MMST. ConclusionThe Mannheim Multicomponent Stress Test increased state anxiety and heart rate but not saliva cortisol. As such, the present results do not support the utility of the Mannheim Multicomponent Stress Test as a viable alternative to The Trier Social Stress Test.