Fat-saturation (FS) pulse sequences can improve the detection of musculoskeletal lesions. We prospectively compared contrast-enhanced T1-weighted FS spin-echo (SE) images, T2-weighted FS fast spin-echo (FSE) images and inversion recovery (IR) FSE images to determine if any of these three pulse sequences is superior for depicting bone marrow and soft tissue lesions. T1-weighted FS-SE images (400-680/10-20 [TR/TE]) after intravenous injection of gadolinium-diethylenetriaminepentaacetic acid (DTPA), T2-weighted FS-FSE (2400-4200/96-112) and IR-FSE (3700-6000/12-14/170 [TR/TE/TI]) images were obtained with a 1.5-T magnet system in 35 patients. The visibility, margination and extent of 37 bone marrow and 67 soft tissue lesions, image uniformity, susceptibility and motion artefacts were qualitatively analysed by four radiologists. The number and size of lesions detected, the mean lesion signal-to-noise ration (S/N) and contrast-to-noise ratio (C/N) were also statistically compared. More bone and soft-tissue lesions were detected on the IR-FSE and T2-weighted FS-FSE than the T1-weighted FS-SE images. The IR-FSE images were significantly better than the T2-weighted FS-FSE and T1-weighted FS-SE images for bone marrow lesions conspicuity (P < 0.01). The soft-tissue lesions were also more conspicuous on the IR-FSE and T2-weighted FS-FSE images than on the T1-weighted FS-SE images (P < 0.005). The lesion extent and image quality were similar on all three sequences while motion artefacts were most severe on the IR-FSE and least severe on the T1-weighted FS-SE images (P < 0.001). Fat saturation was maximal on the IR-FSE images, resulting in a significantly higher mean C/N of bone marrow lesions. The mean C/N of soft-tissue lesions was higher on the T2-weighted FS-FSE images although the differences were not significant. The T2-weighted FS-FSE and IR-FSE sequences are superior to the contrast-enhanced T1-weighted FS-SE sequence for depicting musculoskeletal lesions. Bone marrow lesion conspicuity is greater on the IR-FSE images, with comparable scan time and image quality but more motion artifacts.