Combination antiretroviral therapy (cART) has changed the clinical course of HIV. AIDS-defining conditions (ADC) are suggestive of severe or advanced disease and are a leading cause of HIV-related hospitalizations and death among people living with HIV/AIDS (PLWHA) in the USA. Optimal adherence to cART can mitigate the impact of ADC and disease severity on the health and survivability of PLWHA. The objective of this study was to evaluate the association between ADC at HIV diagnosis and optimal adherence among PLWHA. Using data from the 2008 and 2009 Medicaid data from 29 states, we identified individuals, between 18 and 49 years, recently infected with HIV and with a cART prescription. Frequencies and descriptive statistics were conducted to characterize sample. Univariate and multivariable Poisson regression analyses were employed to evaluate the association optimal cART adherence (defined as ≥ 95% study days covered by cART) and ADC at HIV diagnosis (≥1 ADC) were assessed. Approximately 17% of respondents with ADC at HIV diagnosis reported optimal cART adherence. After adjusting for covariates, respondents with an ADC at HIV diagnosis were less likely to report optimal cART adherence (adjusted prevalence ratio (APR) = 0.64, 95% confidence intervals (CI), 0.54-0.75). Among the covariates, males (APR=1.10, 95% CI, 1.02-1.19) compared to females were significantly more likely to report optimal adherence while younger respondents, 18-29 years (APR=0.67, 95% CI, 0.57-0.77), 30-39 years (APR=0.86, 95% CI, 0.79-0.95) compared to older respondents were significantly less likely to report optimal adherence. PLWHA with ADC at HIV diagnosis are at risk of suboptimal cART adherence. Multiple adherence strategies that include healthcare providers, case managers, and peer navigators should be utilized to improve cART adherence and optimize health outcomes among PLWHA with ADC at HIV diagnosis. Targeted adherence programs and services are required to address suboptimal adherence in this population.