Three-dimensional (3D) wound measurements enable the evaluation of wound healing from the wound bed, which may be a more sensitive measure than traditional two-dimensional (2D) area measurements at the level of the skin surface. Few studies have investigated 3D measurements for monitoring wound healing over time. The aim of this study was to compare the changes in 3D area measurements with traditional (2D) area measurements of diabetic foot ulcers during 8 weeks. Approach: In a prospective cohort study, we monitored the wound healing of 150 diabetic foot ulcers using the 3D-wound assessment monitor camera (3D area) and the digital imaging method (2D area) at baseline, weeks 2, 4, and 8. The following statistical approaches were used to compare the changes in 2D area and 3D area measurements: linear regression analysis, paired Wilcoxon rank test, Bonett-Price 95% confidence interval, and Spearman's correlation coefficient. Results: The overall changes in 3D area were significantly larger compared with 2D area as assessed by Wilcoxon test (p < 0.0001) and Bonett-Price 95% confidence interval of 0.009-0.163. In addition, comparison of 2D area and 3D area measurements showed that the majority of the wounds had larger decrease in 3D area compared with 2D area over time. Innovation: 3D area appears to provide a more sensitive method to monitor wound healing. Conclusion: Our study highlights the potential benefit of a novel 3D camera for monitoring wound healing of diabetic foot ulcers, which was found particularly useful in monitoring wound healing in large wounds. However, in small wounds (<5 cm2), the 2D area and 3D area measurements perform equally well in monitoring the wound healing.