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Abstract Needle biopsy is a common procedure used to diagnose various types of cancer, particularly prostate cancer. Current needle biopsy devices used in this procedure feature End-Cut and Side-Cut needles. They typically have a spring-loaded firing mechanism that leaves uncertainty in controlling the needle position and can damage samples and tissues. Moreover, the sample orientation can be lost. In the Side-Cut needles, the needles cut and damage tissue beyond the sampling region, and the samples are smaller than those collected by End-Cut needles. This paper describes the design and development of a handheld aspiration-assisted device for End-Cut prostate biopsy using a direct current (DC) motor and a lead screw, which allows for better control of needle positioning and target throw length. During the biopsy procedure, the device drives at a constant speed toward the target position, cuts tissue, and utilizes vacuum pressure to retain that tissue. The mechanism helps collect samples while reducing damage to the tissue. Device performance was characterized by testing on ex vivo animal tissue and comparing the performance to two commercial biopsy devices currently used in clinical settings. The evaluation indices were sample mass and length relative to the devices’ throw lengths (End-Cut needle devices) or notch length (Side-Cut needle device). Tests performed on ex vivo bovine cardiac tissue indicated that the developed device collects larger samples compared to the commercial biopsy devices while providing the additional benefits of wider application, sample-orientation marking, and an easy-to-use design.