Objectives: The combination of trastuzumab and chemotherapy has been the standard neoadjuvant treatment for HER2 positive stages IIA–IIIC breast cancer. However, recent clinical trials support the neoadjuvant use of pertuzumab combined with trastuzumab in conjunction with chemotherapy to improve pathological complete response (pCR) rates. Our main objective was to determine whether the trastuzumab-pertuzumab dual blockade in neoadjuvant HER2-positive breast cancer patients achieves higher rates of pCR relative to patients where only trastuzumab was used. Methods: This was a prospective cohort study in patients at San Pedro’s Hospital in Logroño (Spain) with HER2 positive breast cancer who were candidates for neoadjuvant therapy. 39 patients received dual block treatment and were compared with a non-concurrent (retrospective) control group of 39 patients receiving single block treatment. Results: According to the logit model, the coefficient that relates the probability that the pathological response is complete in the case of dual blockade was positive (2.272) and significant at 1% (p-value less than 0.01). The correlation coefficient between radiological and pathological response was 0.87 when we consider dual block treatment. Mucositis was the most frequent adverse effect (29.49% of the sample). There were 3 cardiac events in the single block group and none in the dual block group. Conclusions: The pCR was greater in the dual block group than in the single block group (69.23% versus 25.64%). There was a greater correlation between radiological and pathological response in dual blockade patients. Safety profile was similar in both groups.