Background: Antiretroviral medications have improved the survival and life quality of people living with HIV and turned HIV into a chronic controllable disease. However, the success of HIV treatment depends on many factors; patient adherence is one the most important indicators. In this study, we explored the potential barriers to an effective adherence antiretroviral therapy (ART) among the HIV-positive prisoners of Ghezel-Hesar prison, Iran. Methods: To explore and identify the barriers toward ART adherence, a focus group discussion was held with six prisoners eligible for ART but rejected to be treated or did not retain on ART. The prisoners were recruited through purposive sampling method. All the words, behaviors and even body languages were precisely recorded and analyzed to reach the final results. Results: The most reported obstacles toward ART adherence were the lack of trust in the effectiveness of medications and drug complications. Other reasons were inadequate nutrition, lack of amenities, social stigma, lack of economic and psychological support, misbehavior of prison staff and inadequate methadone prescription for those with opium addiction. Conclusion: Due to the results and the fact that adequate Methadone prescription for opium addiction, improving life quality and receiving emotional and medical support from staff could improve adherence to HIV medication in prisoners,comprehensive education of prisoners about their health condition along with staff education may improve the life condition of HIV infected prisoners and may cause dramatic improvement in ART adherence and prisoners health.