Aim: Lamivudine and zidovudine are nucleoside reverse-transcriptase inhibitors with activity against human immunodeficiency virus type 1 (HIV-1). However, only temporary and limited benefits are observed in HIV-infected patients treated with a single drug or in combination. The limited ability of these agents to decrease viral burden, the rapid development of resistance and toxic side effects have limited their long-term efficacy. Hence, in the present work, an attempt is being made to provide for stable drug delivery system with an improved therapeutic index for both the drugs in the form of stealth liposomes. Methodology: Various liposome batches were prepared by thin film hydration technique and were characterized for preformulation and post formulation parameters such as compatibility, particle size, zeta potential, percentage entrapment, surface morphology, in vitro drug release profile, and stability using specified methods. Results: Fourier transform infrared study indicated that there is no significant chemical interaction between the components. Transmission electron microscopy photograph confirmed that vesicles were homogeneous and spherical in shape. Percentage drug entrapment of stealth liposomes was found to be within the range of 56.21-71.92%. In vitro dissolution was carried out for 24 h and the percentage drug release for all the formulations was in the range of 79.29% and 94.23%. Stability studies showed that the liposomes were stable in âˆ’20Â°C and refrigerated 4Â°C for 1 month without significant changes in drug entrapment. Conclusion: The present study has given us a fair understanding that liposomes with a low amount of cholesterol and long alkyl chain length phosphatidylcholines are a better candidate for stealth liposomes encapsulated with a combination of antiretroviral drugs.