Background: Inefficient operating room (OR) use wastes resources. Studies have suggested “first case on-time starts” (FCOTS) reduce OR “idle time,” yet no direct association between FCOTS and markers of OR efficiency, like “last case on-time end” (LCOTE) or overtime costs, have been reported. We performed this study to evaluate factors associated with FCOTS, LCOTE, and OR overtime costs. Study Design: In April 2017, our medical center launched an FCOTS improvement initiative. Prospectively collected data concerning cases performed in the 6-month pre- (October 2016 to March 2017) and post-intervention (October 2017 to March 2018) periods were retrospectively analyzed. Elective, nontraumatic cases performed by orthopaedics, gynecology, urology, minimally invasive surgery, or colorectal surgery were eligible. Univariate and multivariable analyses were used to evaluate 3 outcomes of interest: the association between FCOTS and LCOTE (primary), the change in FCOTS rates after intervention implementation (secondary), and estimated overtime cost savings associated with FCOTS (secondary). Results: We analyzed 12,073 cases (6,095 pre- vs 5,978 post-intervention) performed over 2,631 OR days (1,401 pre vs 1,230 post). The FCOTS rate increased after intervention (76.1% vs 86.6%, p < 0.001), with post-intervention cases twice as likely to start on time (adjusted odds ratio [aOR] 2.07; 95% CI 1.73 to 2.46, p < 0.001). Additionally, starting on time was associated with a higher likelihood of LCOTE (aOR 1.76; 95% CI 1.38 to 2.24, p < 0.001) and 21.8 fewer overtime minutes (95% CI 13.7 to 29.8, p < 0.001) per OR day. Post-intervention estimated savings of $87,954 in direct OR costs over 6 months were associated with the FCOTS initiative. Conclusions: The FCOTS initiative was associated with higher frequency of FCOTS, which was independently associated with LCOTE. This achieved an estimated 6-month cost savings of more than $80,000 in direct OR expenditures.