Non-contrast cerebral computed tomography (CT) is frequently performed as a first-line diagnostic approach in patients with suspected ischemic stroke. The purpose of this study was to evaluate the performance of hybrid and model-based iterative image reconstruction for standard-dose (SD) and low-dose (LD) non-contrast cerebral imaging by multi-detector CT (MDCT). We retrospectively analyzed 131 patients with suspected ischemic stroke (mean age: 74.2 ± 14.3 years, 67 females) who underwent initial MDCT with a SD protocol (300 mAs) as well as follow-up MDCT after a maximum of 10 days with a LD protocol (200 mAs). Ischemic demarcation was detected in 26 patients for initial and in 64 patients for follow-up imaging, with diffusion-weighted magnetic resonance imaging (MRI) confirming ischemia in all of those patients. The non-contrast cerebral MDCT images were reconstructed using hybrid (Philips "iDose4") and model-based iterative (Philips "IMR3") reconstruction algorithms. Two readers assessed overall image quality, anatomic detail, differentiation of gray matter (GM)/white matter (WM), and conspicuity of ischemic demarcation, if any. Quantitative assessment included signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) calculations for WM, GM, and demarcated areas. Ischemic demarcation was detected in all MDCT images of affected patients by both readers, irrespective of the reconstruction method used. For LD imaging, anatomic detail and GM/WM differentiation was significantly better when using the model-based iterative compared to the hybrid reconstruction method. Furthermore, CNR of GM/WM as well as the SNR of WM and GM of healthy brain tissue were significantly higher for LD images with model-based iterative reconstruction when compared to SD or LD images reconstructed with the hybrid algorithm. For patients with ischemic demarcation, there was a significant difference between images using hybrid versus model-based iterative reconstruction for CNR of ischemic/contralateral unaffected areas (mean ± standard deviation: SD_IMR: 4.4 ± 3.1, SD_iDose: 3.5 ± 2.3, P < 0.0001; LD_IMR: 4.6 ± 2.9, LD_iDose: 3.2 ± 2.1, P < 0.0001). In conclusion, model-based iterative reconstruction provides higher CNR and SNR without significant loss of image quality for non-enhanced cerebral MDCT.