BACKGROUND: Increasing medicines availability and affordability is a key goal of Brazilian health policies. "Farmacia Popular" (FP) Program is one of the government's key strategies to achieve this goal. Under FP, antihypertension (HTN) and antiglycemic (DM) medicines have been provided at subsidized prices in private retail settings since 2006, and free of charge since 2011. We aim to assess the impact of sequential changes in FP benefits on patient affordability and government expenditures for HTN and DM treatment under the FP, and examine their implications for public financing mechanisms and program sustainability. METHODS: Longitudinal, retrospective study using interrupted time series to analyze: HTN and DM treatment coverage; total and per capita expenditure; percentage paid by MoH; and patient cost sharing. Analyzes were conducted in the dispensing database of the FP program (from 2006 to 2012). RESULTS: FP has increased its coverage over time; by December 2012 FP covered on average 13% of DM and 11.5% of HTN utilization, a growth of over 600 and 1500%, respectively. The overall cost per treatment to the MoH declined from R$36.43 (R$ = reais, the Brazilian currency) to 18.74 for HTN and from R$33.07to R$15.05 for DM over the period analyzed, representing a reduction in per capita cost greater than 50%. The amount paid by patients for the medicines covered increased over time until 2011, but then declined to zero. We estimate that to treat all patients in need for HTN and DM in 2012 under FP, the Government would need to expend 97% of the total medicines budget. CONCLUSIONS: FP rapidly increased its coverage in terms of both program reach and proportion of cost subsidized during the period analyzed. Costs of individual HTN and DM treatments in FP were reduced after 2011 for both patients (free) and government (better negotiated prices). However, overall FP expenditures by MoH increased due to markedly increased utilization. The FP is sustainable as a complementary policy but cannot feasibly substitute for the distribution of medicines by the SUS.