Objective Pinhole single-photon emission computed tomography provides superior trade-off between resolution and detection efficiency as compared with conventional parallel-hole collimators for imaging small objects. This study aims to design and evaluate an optimized adaptive multipinhole (MPH) collimator for improved clinical myocardial perfusion single-photon emission computed tomography imaging (MPI) and preclinical small-animal imaging (SAI) of rats based on a clinical scanner. Methods The target resolution and field of view was set to be 1/20 cm for MPI and 0.15/5 cm for SAI, respectively. We determined the design parameters by maximizing the detection efficiency based on system constraints. Point source simulations using Geant4 Application for Emission Tomography were performed for different collimator-to-center of field of view distances to assess the detection efficiency and resolution trade-off. The XCAT phantom with Tc-99m sestamibi distribution and the four-dimensional mouse whole-body phantom with Tc-99m methylene diphosphonate distribution were used to generate noise-free and noisy projections using a three-dimensional analytical MPH projector. Projections were reconstructed using a three-dimensional MPH ordered-subset expectation maximization algorithm. Noise and bias were assessed on the reconstructed images for different collimators. Results The design parameters are (i) 14 pinholes with 3.42 mm aperture size, 14.5 cm collimator-to-detector distance for MPI; (ii) six pinholes with an aperture size of 0.94 mm, 21.2 cm collimator-to-detector distance for SAI. For MPI, the projected full width at half maximum values were 10.68 and 8.19 mm for low energy high resolution (LEHR) and MPH, respectively, whereas MPH had double detection efficiency. For SAI, the projected full width at half maximum values for LEHR and MPH were 4.93 and 1.20 mm, respectively, whereas the detection efficiency of MPH showed 17.5% improvement as compared with LEHR. The noise-bias trade-off improved for MPH as compared with LEHR for both MPI and SAI. The proposed collimator will have adjustable collimator-to-detector distances-that is, 14.5 cm for MPI and 21.2 cm for SAI. Conclusion The new collimator yields substantial improvement in image quality as compared with current MPI using LEHR with extra capability for SAI, bridging the clinical and preclinical imaging based on the same platform.