Background Patient radioprotection in myocardial perfusion imaging (MPI)-SPECT is important but difficult to optimize. The aim of this study was to adjust injected activity according to patient size—weight or BMI—by using a cardiofocal collimator camera. Methods The correlation equation between size and observed counts in image was determined in patients who underwent stress Tc-99m-sestamibi MPI-SPECT/CT with a cardiofocal collimator-equipped conventional Anger SPECT/CT system. Image quality analyses by seven nuclear physicians were conducted to determine the minimum patient size-independent observed count threshold that yielded sufficient image quality for perfusion-defect diagnosis. These data generated an equation that can be used to calculate personalized activity for patients according to their size. Results Analysis of consecutive patients (n = 294) showed that weight correlated with observed counts better than body mass index. The correlation equation was used to generate the equation that expressed the relationship between observed counts, patient weight, and injected activity. Image quality analysis with 50 images yielded an observed count threshold of 22,000 counts. Using this threshold means that the injected activity in patients with < 100 kg would be reduced (e.g., by 67% in 45-kg patients). Patients who are heavier than 100 kg would also benefit from the use of the threshold because although the injected activity would be higher (up to 78% for 150-kg patients), good image quality would be obtained. Conclusions This study provided a method for determining the optimal injected activity according to patient weight without compromising the image quality of conventional Anger SPECT/CT systems equipped with a cardiofocal collimator. Personalized injected activities for each patient weight ranging from 45 to 150 kg were generated, to standardize the resulting image quality independently of patient attenuation. This approach improves patient/staff radioprotection because it reduces the injected activity for < 100-kg patients (the majority of patients).