Expressive writing has been linked to positive psychological and health outcomes in general and medical populations, but research examining this intervention in HIV is limited. Higher levels of emotional expression (EE) and depth processing (DP) during writing have been linked to better health status in HIV. Expressive writing has been shown to improve health-related quality of life (HRQoL) in other populations, but has not been examined in HIV. HRQoL is often compromised in HIV+ individuals and therefore improvements in this area are an appropriate goal of psychosocial interventions. This longitudinal study used HLM analyses to examine the relationship between levels of EE and DP during trauma writing and the rate of change in HRQoL over six months in an ethnically diverse sample of 106 HIV+ men and women. Three subscales of the HIV/AIDS-targeted Quality of Life measure were examined: Overall Healthy Functioing (HRQoL-Overall), Without Health Worries (HRQoL-Health), and Life Satisfaction (HRQoL-Life). All longitudinal analyses controlled for demographic (age, gender, race/ethnicity, education), medical (CD4 and VL) and psychological (stressful life events) factors. No significant effects were found for EE/DP to predict changes in HRQoL over time for the full sample. When men and women were examined separately, there was a non-significant tendency for men to decrease in HRQoL over time and for women to increase over time, and a number of EE/DP variables were significant predictors of rate of change in HRQoL. As hypothesized, for women (n = 44) higher level of Experiential Involvement DP predicted greater increase in HRQoL-Overall and HRQoL-Life, and higher negative EE also predicted greater increase in HRQoL-Life over time. Opposite of the direction hypothesized, higher Self Esteem DP predicted a lower level of increase in HRQoL-Life for women. For men (n = 62), findings appeared to be in the opposite direction of women, with greater Self Esteem DP working as a buffer to decreases in HRQoL-Life and HRQoL-Health over time. Furthermore, higher Experiential Involvement and negative EE appeared detrimental for men as both predicted greater decreases in HRQoL-Life over time and Experiential Involvement also predicted greater decreases in HRQoL-Health. Results should be interpreted with caution, as the overall slopes did not show significant change in HRQoL over time. The reasons for observed gender differences are not known. This is the first study to examine the impact of EE and DP in expressive trauma writing on HRQoL in HIV+ individuals. Implications and limitations are discussed.