In 2013, a change in copayment rate was introduced in the Basque Country (one year later than in the other regions in Spain), and improvements were made to drug packaging. In 2014, a National Program Against Bacterial Resistance (Spanish abbreviation: PRAN) was approved. The aim of this study is to analyze the impact of change to the copayment rate, the adjustment of drug packaging, and the approval of PRAN on the consumption of antibiotics. Raw monthly data on the consumption of antibiotics (costs, packages, and daily defined doses per thousand people (DID)) were collected from January 2009 to December 2018 in the Basque Country. Counterfactual and intervention analysis (Autoregressive integrated moving average (ARIMA) model) was performed for the total series, disaggregated by group of antibiotics (2019 WHO Access, Watch, and Reserve (AWaRe) Classification) and active substances with the highest cost per prescription (cefditoren and moxifloxacin), the lowest cost per prescription (doxycycline and cloxacillin), and the most prescribed active ingredients (amoxicillin, azithromycin, and levofloxacin). Introduction of copayment led to a ‘stockpiling effect’ one month before its implementation, equal to 8% in the three consumption series analyzed. Only the adjustment of drug packaging significantly reduced the number of packages dispensed (−12.19%). PRAN approval reduced consumption by 0.779 DID (−4.51%), representing a significant decrease for both ’access’ and ’watch’ group antibiotics. Despite the delay in implementing changes to copayment, there was a ‘stockpiling effect’. With the adjustment of packaging, fewer packs were prescribed but with a higher drug load and price. PRAN approval reduced both the consumption of ’access group antibiotics’ (first-line treatment) and ’watch group antibiotics’ (second-line treatment).