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Studies concerning persons living with HIV (PLWH) report that stressful life events (SLEs) contribute to an exacerbation of symptoms and reduced antiretroviral (ARV) adherence and quality of life (QOL). Little is known about whether these findings are site-specific. Our study's aims were to characterize the type and frequency of SLEs for PLWH in Puerto Rico, South Africa, and the United States, and to assess the impact of SLEs by national site, symptoms, and ARV adherence concerns on QOL. The sample consisted of 704 participants. The total number of SLEs correlated significantly with the total number of symptoms, adherence concerns, and QOL (p ≤ .001). Overall, 27.2% of the variance in QOL was explained by the aforementioned variables. Although SLEs were of concern to PLWH, worries about ARV adherence were of even greater concern. Routine assessment of ARV concerns and SLEs can promote …