Several health interventions have been put in place to improve health outcomes of people living with HIV/AIDS (PLHIV) in Ghana. We evaluated the impact of Antiretroviral Therapy (ART) on all-cause mortality in Ghana using matching procedures. This was a retrospective cohort study of 12,881 HIV/AIDS patients initiated on ART at 40 sentinel sites and 199 treatment centers between 2013 and 2016 countrywide. Patients were included if they had date of ART initiation and if they had mortality outcome recorded. Mahalanobis distant metric matching within propensity score caliper and other matching procedures were used to evaluate the effectiveness of ART in reducing the risk of all-cause mortality among PLHIV in Ghana. We performed sensitivity analysis using different matching procedures including Kernel weighting adjustment and Mahalanobis distance metric matching with nearest neighbour to ascertain the robustness of our results in the presence of unmeasured covariates. The proportion of patients on ART was 60.3% (95% CI: 59.5-61.1). The total number of mortalities reported was only 734 representing 4.6% (95% CI: 4.2-4.9) of the studied population. The risk of all-cause mortality has reduced by 11.6 percentage point among HIV/AIDS patients who were on ART compared to those who were not on ART (95% CI: 9.6-13.4). ART was associated with a decreased risk of all-cause mortality. Effort being made by Government and non-Governmental organizations in support of ART treatment in Ghana should continue unabated to help reduce mortality rate and improve health outcomes among HIV/AIDS. To reduce bias to the barest minimum between treatment and intervention group when evaluating the effectiveness of health interventions, it is recommended to use matching procedures especially when the study design is not a randomized control trial.