Objective Aortic cross-clamp and cardiopulmonary bypass times are independent predictors of postoperative morbidity and mortality. Reducing ischemic times with automated titanium fasteners may improve surgical outcomes. This study compared operative times and costs of titanium fasteners versus hand-tied knots for prosthesis securement in open aortic valve replacement. Methods A randomized control trial was conducted during a 16-month period at a single university medical center. Patients undergoing elective aortic valve replacement were randomized to the titanium fastener (n = 37) or hand-tied groups (n = 36). Knotting, aortic cross-clamp, cardiopulmonary bypass, and total operating room times were recorded. Hospital charges were also calculated for these procedures. Results Baseline characteristics, concomitant procedures, prosthetic valve size, and sutures were similar between groups. The titanium fastener group had significantly reduced knotting (7.4 vs. 13.0 minutes, P < 0.001), aortic cross-clamp (69 vs. 90 minutes, P < 0.05), cardiopulmonary bypass (86 vs. 114 minutes, P < 0.05), and total operating room times (234 vs. 266 minutes, P < 0.05). Intraoperative complications occurred more frequently in the hand-tied group compared with the titanium fastener group. Postoperative complications were similar between groups. Operating room costs were significantly higher in the titanium fastener group (US $10,428 vs. US $9671, P = 0.01). Hospitalization costs did not differ significantly between the titanium fastener and hand-tied group (US $23,987 vs. US $21,068, P = 0.12). Conclusions Titanium fastener use was associated with shorter knotting, aortic cross-clamp, cardiopulmonary bypass, and operating room times and fewer intraoperative complications in open aortic valve replacement, without significantly increasing hospitalization cost.