In this study, the response surface methodology and the Box-Behnken design were used to help optimize the availability rate, performance, and quality of the inhaler spray production line at Sina Pharmaceutical Laboratories Company in order to maximize the overall equipment effectiveness index. For this purpose, the actual results of the production line were analyzed in two separate designs and in two stages. In the first stage, the results obtained from the production line for a period of 32 months were analyzed through a full factorial design with three factors of availability rate, performance, and quality at three levels of the highest (+1), average (0), and lowest (-1) in the production line. The results from the first stage showed that in this case, to maximize the productivity rate of the overall equipment effectiveness index of the production line, the availability, performance, and quality rates should be in the state of (1+) and the overall equipment effectiveness index will be 100 percent, but all experts agree that in the real world, the efficiency of the production line will never be 100 percent in a 32-month period; Therefore, in the second stage, in order to actually optimize the overall equipment effectiveness index rate using the response surface methodology and the Box-Behnken design, the availability, performance, and quality rates for the independent parameters were 100%, 90%, and 99.91%, respectively, and the overall equipment effectiveness index in the second stage was 89.92%. Based on the results obtained, the availability and efficiency of the production line had an impact on the productivity of the inhaler spray production line, while the quality index had a lesser impact. The overall equipment effectiveness index rates, availability, performance, and actual quality of the inhaler spray production line in Sina Pharmaceutical Laboratories Company were 67.16%, 86.84%, 75.66%, and 99.91%, respectively. Practical suggestions have been provided to the company to achieve the optimal level of the mentioned parameters, assuming stability in the quality parameter of the production line.