The recovery of petroleum resources from previously untapped shale reserves plays an important role in the global energy market. Effective management of limited water resources and control of microbial contamination in all process fluids are critical to the sustained quality of production fluids. Microbiological contamination in untreated waters is recognized in the oil and gas industry as posing high risk of production fluid souring by allowing growth and metabolism of sulfate reducers. In addition to hydraulic source water contamination it is expected that microbes can be introduced into shales at the time of drilling necessitating treatment of source waters in order to target existing downhole contamination.A two part biocide treatment strategy has been extensively evaluated in controlled laboratory studies. The synergistic combination treatment involves the co-injection of dimethyl oxazolidine (DMO) along with the industry benchmark glutaraldehyde (Glut). Lab testing showed a combination treatment applied at a 1:4 Glut to DMO active ratio was highly synergistic against bacteria. This ratio provided both rapid kill of sulfate reducing bacteria (SRB) and acid producing bacteria (APB) as well as achieving extended control in downhole conditions. Testing conditions were designed to simulate downhole conditions in a North American shale play and subsequently the shale play was selected for field trials.A field wide application of Glut:DMO in the Niobrara formation took place from to 2012-2013. This case study reports 72 hydraulically fractured wells comprised from 25 well pads that received the Glut/DMO combination treatment. The treatment was successful in maintaining low bacteria counts in the flowback/produced water using liquid culture media (3 positive APB/SRB vials or less). Key advantages of this new treatment strategy include lower total biocide usage versus competitive biocides improved environmental (ecotoxicity) profile enhanced performance at alkaline pH and compatibility with process additives.