Suboptimal adherence to Antiretroviral Therapy (ART) regimens can lead to the development of drug resistance, virologic and clinical failure, and, on the community level, the spread of drug-resistant HIV. To design effective interventions, it is crucial to understand locally specific barriers to optimal adherence. Self-report data from a cross-sectional sample of 527 adherence-challenged people living with HIV (PLWH) in the South-Indian state of Karnataka showed that they took on average 68% of prescribed doses in the past month. Large majorities of participants encountered individual (95%), social/structural (88%), and clinic/regimen (80%) adherence barriers. Multivariate linear regression analyses of past month adherence showed that disclosure to all adults in the household was positively related to adherence, as was employing a larger number of adherence strategies, perceiving more benefits of ART, and having been on ART for longer. Fears of stigmatization upon disclosure of HIV-status to friends and people at work were negatively related to adherence. These results suggest that some barriers, especially individual-level barriers like forgetfulness are very common and can be targeted with relatively simple individual-level strategies. Other barriers, related to fear of stigma and lack of disclosure may require family- or community-level interventions.