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Mexico started scaling-up access to antiretroviral treatment in the late 1990s. Even though the Mexican Health System enrolled patients at impressive speed, in the initial years important aspects of the quality of care were overlooked.To describe antiretroviral prescribing and adherence practices in Mexico during initial scaling-up of antiretroviral treatment in comparison to national treatment guidelines and to estimate the associated economic cost.Eleven public sector hospitals provided detailed patient chart data. Monthly observations formed the basis of scenarios aligned by calendar month and by month before and after initiation of triple therapy. The scenarios varied by extent of prescription refill, adherence levels, and compliance with national treatment guidelines.Antiretroviral therapy prescription practices were largely inconsistent with published guidelines. Non-recommended combinations were prescribed to between 54 and 79% patients-months per year. Additionally, more than 50% of patients experienced four to 13 changes in treatment. Modeling of the economic impact of treatment practices showed that it would have been possible to effectively treat the same number of patients at the same or lower cost per patient.In addition to dispensing drugs, countries scaling-up antiretroviral therapy must find ways to ensure consistent drug supply, appropriate prescription practices and effective levels of adherence. Failing to do so will seriously reduce treatment effectiveness, greatly increasing the cost per unit of health benefit. With very low levels of effective adherence patients may even be harmed and the spread of multi-drug resistant virus facilitated.