In this study, we prove that the mass die-offs occurring in conjunction with red adductor disease in pearl oysters are caused by an infection. Our research also reveals the influence of water temperature on the onset of the disease and its progress, and we propose measures that are effective in mitigating harm from the disease. To analyze the effect of water temperature on the onset and progress of the disease, laboratory infection experiments were performed over a range of water temperatures (13 °C–31 °C). The experiments showed that disease onset and progress were highly dependent on water temperature. No outbreak was observed at temperatures below 16 °C, while the adductors of experimentally infected oysters turned red in a short time at temperatures between 19 °C and 31 °C. Our research showed that the cumulative water temperature value for days when water temperature was above 19 °C (AT 19 = Σ( T i), T i > 19) is an effective numerical indicator for the onset of red adductor disease. We also found that when pearl oysters already infected with red adductor disease at a high rate are kept at water temperatures below 16 °C in the winter for a certain minimum period of time, clinical signs regress, and that this treatment is also effective in delaying relapses of the disease with rising water temperatures in the spring. We determined a numerical indicator for finding the low-temperature index that is most effective in delaying disease onset. This is the low-temperature burden based on the number of days with water temperatures of 16 °C or below and those days' temperatures (LTI 16 = Σ(16 − T i), T i < 16 °C). We found that the larger the LTI 16 value, the greater the effectiveness in suppressing the onset of red adductor disease. Hence, appropriate low-water-temperature management in the winter helps prevent the relapse and progress of the disease in the spring and beyond when water temperature rises. Results of this research strongly suggest that the LTI 16 value in wintering fisheries and the cumulative water temperature of the days in spring and beyond when the water temperature is above 19 °C (AT 19) make it possible to predict when red adductor disease will break out in pearl oysters, and therefore help efforts to mitigate damage from relapses.