Neoadjuvant therapy (NAT) has become increasingly common in pancreatic ductal adenocarcinoma (PDAC). Still, PDAC remains one of the deadliest cancers and clinically useful biomarkers are needed. Matrix metalloproteinase 8 (MMP-8) has previously been identified as a potential biomarker for PDAC patients undergoing up-front surgery. We investigated the prognostic significance of MMP-8 in PDAC patients treated with NAT and evaluated the association of MMP-8 expression to treatment response. We studied MMP-8 expression using immunohistochemistry in a tissue microarray with samples from 115 NAT and 144 up-front surgery patients. We examined NAT response from resection specimens by estimating the amount of residual tumour cells. We analysed the association of MMP-8 immunoexpression with survival and treatment response. High MMP-8 immunoexpression associated with better survival among patients with strong NAT response (HR 0.22, CI95% 0.05-0.86, p = 0.030). This association was not observed among patients with poor NAT response nor in the overall NAT group. Furthermore, MMP-8 expression did not differ significantly between the NAT and up-front surgery groups. In conclusion, the MMP-8 tissue expression after NAT is a protective biomarker in PDAC patients with strong NAT response but fails to associate with favourable prognosis in patients with poor NAT response.