Misdiagnosis can occur when different case definitions are used by clinicians (relative misdiagnosis) or when failing the genuine diagnosis of another disease (misdiagnosis in a strict sense). In complex diseases, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), this problem translates to a recurrent difficulty in reproducing research findings. To explore these effects, we simulated data from case-control studies under the assumption of misdiagnosis in a strict sense. We estimated the power to detect a genuine association between a potential causal factor and ME/CFS and demonstrated how current research studies may have suboptimal power. To address the implications of these findings, suggestions for how power can be improved are given and explained within the context of the disease.