Male factory workers in China are vulnerable to HIV transmission. Commercial and nonmarital noncommercial contacts are the driving forces of heterosexual HIV transmission among male factory workers in China. There is a lack of effective HIV interventions for male factory workers in China.The primary objective of this randomized controlled trial was to compare the efficacy of an enhanced versus the standard version of a WeChat mini program in reducing sexual intercourse with nonregular female sex partners and female sex workers among male factory workers in Shenzhen, China.A nonblinded 2-arm parallel randomized controlled trial was conducted between December 2021 and April 2023. Participants were adult male factory workers in Shenzhen who had access to a smartphone and WeChat. Those who had oral or anal sex with a man or self-reported as HIV positive were excluded. A total of 247 participants were randomly assigned to the intervention group (n=125, 50.6%) or the control group (n=122, 49.4%); 221 (89.5%) and 220 (89.1%) completed follow-up surveys at T1 (6 months after completion of the interventions) and T2 (6 months after T1). Participants in the control group had access to the standard WeChat mini program that provided basic HIV-related knowledge and information about local free HIV testing services. Participants in the intervention group had access to the enhanced WeChat mini program. The enhanced mini program covered all the information in the standard mini program. In addition, the enhanced mini program assessed users' behaviors and invited users to watch different web-based videos on reducing nonmarital sexual contacts and promoting HIV testing based on their behavioral characteristics at months 0 and 1. The videos were developed based on in-depth interviews with male factory workers. Intention-to-treat analysis was used for outcome analyses. Multiple imputation was used to replace missing outcome values at T1 and T2.At T1, fewer participants in the intervention group reported sexual intercourse with a nonregular female sex partner in the past 6 months compared with the control group (1/125, 0.8% vs 8/122, 6.6%; relative risk=0.12, 95% CI 0.02-0.96; P=.02). However, there were no between-group differences in sexual intercourse with a nonregular female sex partner at T2 (10/125, 8% vs 14/122, 11.5%; P=.36) or sexual intercourse with a female sex worker at T1 (2/125, 1.6% vs 2/122, 1.6%; P=.98) or T2 (8/125, 6.4% vs 8/122, 6.6%; P=.96).The enhanced WeChat mini program was more effective than the standard WeChat mini program in reducing sexual intercourse with nonregular female sex partners among male factory workers in the short term but not in the longer term. Improvements should be made to the WeChat mini program before implementation.ClinicalTrials.gov NCT05811611; https://clinicaltrials.gov/study/NCT05811611.©Kechun Zhang, Bolin Cao, Yuan Fang, Xue Liang, Danhua Ye, Ya Qi Chen, Ruilan Zhong, He Cao, Tian Hu, Ting Li, Yong Cai, Huachun Zou, Zixin Wang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 09.09.2024.