Virtual Manipulatives (VMs) are computer-based, dynamic, and visual representations of mathematical concepts, provide interactive learning environments to advance mathematics instruction (Moyer et al., 2002). Despite their broad use, few research explored the integration of VMs into mathematics instruction (Moyer-Packenham & Westenskow, 2013). To fill this gap, this experimental study examined the impact of using VMs with two different instructional approaches on students' learning of slope. Participants were 48 college students taking a remedial mathematics course, randomly assigned into two groups, and used the same set of VMs with open-ended exploratory versus structured mathematics questions. The pre-and posttest assessing students' knowledge of slope were administered and students' interactions with VMs were analyzed. The results revealed that students using VMs with exploratory learning activities substantially improved their conceptual knowledge of slope, whereas students working with VMs to solve structured mathematics questions displayed considerable growth in their procedural and combined conceptual and procedural knowledge of slope.