There is a lack of scientific testing of commercially available malware detectors, especially those that boast accurate classification of never-before-seen (i.e., zero-day) files using machine learning (ML). The result is that the efficacy and trade-offs among the different available approaches are opaque. In this paper, we address this gap in the scientific literature with an evaluation of commercially available malware detection tools. We tested each tool against 3,536 total files (2,554 or 72% malicious, 982 or 28% benign) including over 400 zero-day types of malware, and tested with a variety of file types and protocols for delivery. Specifically, we investigate three questions: (1) Do ML-based malware detectors provide better detection than signature-based detectors?; (2) Is it worth purchasing a network-level malware detector to complement host-based detection?; and (3) What is the trade-off in detection time and detection accuracy among commercially available tools using static and dynamic analysis? We present statistical results on detection time and accuracy, consider complementary analysis (using multiple tools together), and provide a novel application of a recent cost–benefit evaluation procedure by Iannaconne & Bridges that incorporates all the above metrics into a single quantifiable cost to help security operation centers select the right tools for their use case. Our results show that while ML-based tools are more effective at detecting zero-days and malicious executables, they work best when used in combination with a signature-based solution. In addition, network-based tools had poor detection rates on protocols other than the Hypertext Transfer Protocol (HTTP) or the Simple Mail Transfer Protocol (SMTP), making them a poor choice if used on their own. Surprisingly, we also found that all the tools tested had lower than expected detection rates, completely missing 37% of malicious files tested and failing to detect any polyglot files.