Objectives. We examined findings from a randomized controlled intervention trial designed to improve the quality of life of people living with HIV in Thailand. Methods. A total of 507 people living with HIV were recruited from 4 district hospitals in northern and northeastern Thailand and were randomized to an intervention group (n=260) or a standard care group (n=247). Computer-assisted personal interviews were administered at baseline and at 6 and 12 months. Results. At baseline, the characteristics of participants in the intervention and standard care conditions were comparable. The mixed-effects models used to assess the impact of the intervention revealed significant improvements in general health (B=2.51; P=.001) and mental health (B=1.57; P=.02) among participants in the intervention condition over 12 months and declines among those in the standard care condition. Conclusions. Our results demonstrate that a behavioral intervention was successful in improving the quality of life of people living with HIV. Such interventions must be performed in a systematic, collaborative manner to ensure their cultural relevance, sustainability, and overall success.