Background Growing evidence indicates tissue inhibitors of matrix metalloproteinases (TIMPs) as potential players in inflammatory bowel disease (IBD), but, no prospective data are available in IBD remission/relapse. Material & methods In this prospective pilot study, a cohort of IBD patients (n = 32) was enrolled and treated with monoclonal anti‐TNF‐α antibodies. Patients were clinically followed up for a median period of 54 weeks. Serum circulating levels of C‐reactive protein (CRP), TIMP‐1 and ‐2, matrix metalloproteinase (MMP)‐9 and ‐8, myeloperoxidase (MPO) and neutrophil elastase (NE) were assessed by ELISA at enrolment and at the end of the treatment. Results The percentage (%) TIMP‐2 reduction from baseline to end of treatment was independently associated with IBD remission at the end of treatment and follow‐up as well. ROC curve analysis further confirmed the good prognostic accuracy of % TIMP‐2 reduction over the treatment period. Conversely, no other change in inflammatory molecule concentrations was able to predict short‐ or long‐term IBD remission. Conclusions This study indicates TIMP‐2 reduction during IBD treatment with monoclonal anti‐TNF‐α antibodies as a potential prognostic parameter of short and long term remission. To understand if TIMP‐2 is an innocent biomarker or an active pathophysiological factor in IBD remains to be clarified.