OBJECTIVE: To assess the time-dependent effects of Panax ginseng on health-related quality of life (HRQOL) using a general health status questionnaire. METHODS: Subjects were randomized in a double-blind manner to 200 mg Panax ginseng (n=15) or placebo (n=15) daily for 8 weeks. The Short Form-36 version 2 (SF-36v2), a validated general health status questionnaire, was used to assess HRQOL at baseline, 4 and 8 weeks. HRQOL between the groups was compared using repeated measures analysis of covariance. A p-value of <0.05 was considered statistically significant. RESULTS: There were no significant differences in baseline demographics and SF-36v2 scores between the groups. After 4 weeks of therapy, higher scores in social functioning (Panax ginseng: 54.9±4.6 vs. placebo: 49.2±6.5; p=0.014), mental health (Panax ginseng: 52.2±7.7 vs. placebo: 47.2±7.3; p=0.075) and the mental component summary (Panax ginseng: 51.3±7.4 vs. placebo: 44.3±8.3; p=0.019) scales were observed in patients randomized to Panax ginseng; these differences did not persist to the 8-week timepoint. No other significant differences in HRQOL between the groups were found at the 4- and 8-week timepoints. The incidence of adverse effects was 33% in the Panax ginseng group compared to 17% in the placebo group (p=0.40). Subjects given Panax ginseng (58%) were more likely to state that they received active therapy than subjects given placebo (17%; p<0.05). CONCLUSIONS: Panax ginseng improves aspects of mental health and social functioning after a 4 weeks of therapy although these differences attenuate with continued use.