Background: The management of disposable and reusable supplies might have an impact on the cost efficiency of the Operating Room (OR). This study aimed to evaluate the cost and reasons for wasted supplies in the OR during surgical procedures. Methods: We conducted an observational and prospective study in a French university hospital. We assessed the cost of wasted supplies in the OR (defined by opened unused devices), the reasons for the wastage, and the circulator retrievals. At the end, we assessed the perception of surgeons and nurses relative to the supply wastage. Results: Fifty routine procedures and five non-scheduled procedures were observed in digestive (n = 20), urologic (n = 20) and gynecologic surgery (n = 15). The median cost [IQR] of open unused devices was €4.1 [0.5; 10.5] per procedure. Wasted supplies represented up to 20.1% of the total cost allocated to surgical supplies. Considering the 8000 surgical procedures performed in these three surgery departments, the potential annual cost savings were 100 000€. The most common reason of wastage was an anticipation of the surgeon's needs. The circulating nurse spent up to 26.3% of operative time outside of the OR, mainly attending to an additional demand from the surgeon (30%). Most of the survey respondents (68%) agreed that knowing supply prices would change their behavior. Conclusions: This study showed the OR is a major source of wasted hospital expenditure and an area wherein an intervention would have a significant impact. Reducing wasted supplies could improve the cost efficiency of the OR and also decrease its ecological impact.