Women with chronic conditions such as HIV or non-communicable diseases face unique challenges affecting their adherence to therapeutic regimens and quality of life (QoL). Limited compliance often leads to suboptimal outcomes. The present study aimed to assess the level of compliance with therapeutic regimens and health-related QoL among women ageing with and without HIV, and to explore associations between demographic and clinical variables. A descriptive cross-sectional study was conducted among 200 women (100 with HIV and 100 without HIV) aged 40-60 years, attending outpatient clinics in Chennai. Compliance and health-related QoL (HRQoL) were assessed using a rating scale and the SF-36 Survey. Data were analysed using descriptive and inferential statistics, including Pearson’s correlation and chi-square tests. Women with HIV demonstrated higher compliance (100%) compared to women without HIV (92%). HRQoL was also higher among women ageing with HIV; majority of women (92%) ageing with HIV had a good level, and 8 percent had a fair level of HRQoL. Whereas, among women ageing without HIV, 71 percent had a good level and 29 percent had a fair level of HRQoL. A moderate positive correlation was found between compliance and HRQoL (r = 0.434, p < 0.001 for women with HIV; r = 0.593, p < 0.001 for women without HIV). It is concluded that effective adherence to therapeutic regimens positively impacts HRQoL among women ageing with chronic conditions. Targetted interventions focusing on compliance and holistic care are essential to improve health outcomes.