The effect of perceived stigma on the variables of healthcare self-efficacy and treatment adherence behavior was examined in three chronic diseases of differing levels of stigmatization (HIV - high, type II diabetes - moderate, and hypertension - low), each requiring continuous adherence to a medication treatment regimen. Ninety subjects (30 in each disease group) participated. The hypothesis that perceived stigma would mediate the effect of disease group on treatment adherence and adherence self-efficacy in direct negative proportion to the differing level of stigma perceived by each group was tested using Baron & Kenny's three-step mediational analysis of covariance. No statistical support was found for the hypothesized declining linear trend in the mean scores of treatment adherence and self-efficacy, moving from the hypertension group, to the diabetes group, to the HIV group. However, when the two "more stigmatized" groups (HIV and diabetes) were pooled and compared to the "less stigmatized" group, (hypertension), the hypertension group did report significantly higher levels of treatment adherence and self-efficacy, confirming the hypothesis. A linear increase in the levels of mean perceived stigma across the three disease groups was confirmed, with the HIV group reporting the highest level of perceived stigma, followed by the diabetic group, and lastly the hypertension group. When the variable of perceived stigma was controlled for as a covariate in the third step of the analysis, the significant difference between "more" and "less stigmatized" disease groups in levels of the treatment adherence - self-efficacy composite variable was no longer found, verifying that perceived stigma mediated or caused the significant negative effect of disease group on the outcome variables. The results provide quantitative, empirical evidence that chronic disease stigma can have a direct negative impact on treatment adherence and adherence self-efficacy, supporting existing primarily qualitative research suggesting this. The study hopes to inform the development of clinical and psychosocial interventions to optimize treatment adherence for individuals living with a stigmatized chronic disease.