Betel quid (BQ), chewed by about 600 million people worldwide, is one of the most widely used addictive substances. Little is known about psychological factors in BQ chewers. The present study was the first attempt to explore the relationships between BQ chewing, personality, and mood. A survey was conducted with a purposive sample to assess BQ chewing habits in four subgroups: BQ-only users, BQ users who smoke and/or drink, smokers and/or drinkers only, and substance nonusers. A total of 494 participants were recruited from the civilian, non-institutionalized population in Taiwan. Habitual consumption of BQ, smoking and drinking; socio-demographic variables; extraversion; and mood (tension, depression, anger, vigor, fatigue, confusion, and self-esteem). All BQ chewers were evaluated on BQ dependence domains using DSM IV and ICD-10 criteria. The 6-month BQ dependency rate among BQ chewers, defined by either DSM-IV or ICD-10 criteria, ranged from 42.9 to 45.6%. BQ-only users had significantly lower scores on extraversion than substance nonusers. BQ-only users had statistically significant higher scores on confusion and total mood than substance nonusers. BQ-only users had significantly higher scores on fatigue, anger, tension, and depression, than substance nonusers, BQ users who smoke and/or drink, and smokers and/or drinkers only. The number of BQ dependence domains correlated significantly negatively with total mood scores. Conclusions/Importance: The results supported the two hypotheses: (a) BQ chewing is associated with low extraversion; and (b) BQ chewing is related to negative mood.