Objective To review a quality control and quality assurance (QC/QA) model established to ensure the validity and reliability of collection, storage, and analysis of biological outcome data, and to promote good laboratory practices and sustained operational improvements in international clinical laboratories. Methods A two-arm randomized community-level HIV behavioral intervention trial was conducted in five countries: China, India, Peru, Russia, and Zimbabwe. The trial was based on diffusion theory utilizing a Community Popular Opinion Leaders (C-POL) intervention model with behavioral and biological outcomes. The model was established by the Biological Outcome Workgroup (BOWG), which collaborated with the Data Coordinating Center (DCC) and John Hopkins University Reference Laboratory. Five international laboratories conducted Chlamydia/gonorrhea PCR, HSV2 EIA, Syphilis RPR/TPPA, HIV EIA/Western Blot, and trichomonas culture. Data were collected at baseline, 12, and 24 months. Results Laboratory performance and infrastructure improved throughout the trial. Recommendations for improvement were consistently followed. Conclusions Quality laboratories in resource-poor settings can be established, operating standards can be improved, and certification can be obtained with consistent training, monitoring, and technical support. Building collaborative partnership relations can establish a sustainable network for clinical trials, and can lead to accreditation and international laboratory development.