Purpose: Real-time compound imaging is one of the main advances in monographic technology. Our aim was to assess the potential benefits of real-time compound sonography in the fine needle aspiration biopsy of the thyroid nodules compared with conventional sonography. Methods: Sonography-guided fine needle aspiration biopsy was performed on 60 thyroid nodules of 60 consecutive patients. Sonograms of the same nodule were obtained during the biopsy procedure using both conventional sonography and compound imaging. All images were independently reviewed by two independent observers experienced in sonography. For all images, the visibility of the needle shaft, visibility of the needle tip, and overall image quality were assessed and graded. Wilcoxon's signed rank test was used for statistical comparisons between the two techniques. Kappa scores were calculated to assess inter-observer agreement. Results: Real-time compound imaging was significantly superior to conventional sonography with respect to overall image quality, and visibility of the needle shaft and the tip, compared to conventional sonography (p < 0.001 for all evaluated parameters). In none of the images was the visibility of needle tip better in conventional images according to both observers. Conclusion: In terms of overall image quality, and the visibility of the shaft and tip of the needle, real-time compound sonography is superior to fundamental sonography in guiding the biopsy needle ultrasonographically. We assume that real-time compound imaging can be used for guidance in fine needle aspiration biopsy, and may be especially helpful for less experienced radiologists by way of easier visualization of the needle and its relationships with the lesion and neighboring structures.