Synaesthesia has long been considered a benign alternative form of perception most often associated with positive rather than negative outcomes. The condition has been associated with a variety of cognitive and perceptual advantages, including benefits in memory, processing speed, and creativity. It is not currently recognized in the DSM-IV. Recently, however, several studies have raised the question of a possible link between synaesthesia and clinical conditions. Here, we present the first large-scale screening of the general population in which we (1) objectively identified grapheme-colour synaesthetes and (2) elicited information from our participants about a range of clinical conditions. We compared the prevalence rates of these conditions in synaesthetes versus nonsynaesthetes to establish whether any conditions were found at a higher rate among synaesthetes. In our initial study, screening 3,742 people (95 synaesthetes and 3,647 controls), we found initially that grapheme-colour was significantly comorbid with two conditions (anxiety disorder and obsessive compulsive disorder). In our second study, screening a new population of 120 synaesthetes and 166 non-synaesthetes, we replicated our finding that grapheme-colour synaesthesia is comorbid with anxiety disorder. At the same time, we also addressed a methodological concern that likely elevated rates of OCD in Study 1. We consider the aetiology of synaesthesia to determine whether there may be a shared genetic or neurological basis with anxiety disorder, and we question the status of synaesthesia within a mental health framework.