Very few studies have documented relations between personality traits and quality of life among individuals living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). Some have shown that poor perceived quality of life as determined by a sense of purpose may be associated with inadequate adherence to highly active antiretroviral treatment (HAART) in this population. Although adequate HAART adherence is critical to achieve the full therapeutic effects of newly and highly effective regimens, very little is known of how both personality factors and HIV-specific quality of life may impact adherence to these medication regimens. This study evaluated relations among personality traits, quality of life and HAART adherence among 116 men and women living with HIV/AIDS. Results showed that personality traits such as neuroticism were significantly associated with poorer quality of life, whereas conscientiousness and extraversion were associated with better quality of life. In contrast, personality traits were not directly related to HAART adherence. Both higher overall functioning and lower medication worries scores were significantly associated with HAART adherence. Findings suggest that personality traits are associated with HIV-specific quality of life on the one hand, and that HIV-specific quality of life is related to HAART adherence on the other. Future studies assessing the efficacy of psychosocial interventions in improving quality of life and HAART adherence should consider the role of personality traits in promoting better quality of life.