Purpose: This study investigated the influence of hard and resilient polymerized acrylic resin base materials on the blood flow of the supporting underlying mucosa of mandibular denture wearers during different denture-wearing periods. Materials and Methods: Measurements were carried out on 20 complete denture wearers, 10 with hard bases and 10 with soft ones. The mucosal blood flow underlying the dentures was measured bilaterally in the canine and molar regions using a laser Doppler flowmeter. Baseline measurements were performed before denture wearing and after the dentures were worn for 1 week, 1 month, 3 months, and 6 months. Results: Mean blood flow to the mucosa after 1 week was significantly lower in the measured regions than that obtained before the dentures were worn. Blood flow in the canine region returned to almost normal levels 6 months after beginning to wear complete dentures. However, blood flow in the molar region of the denture wearers in the hard base group increased after 6 months, whereas blood flow values did not return to the levels recorded before denture insertion in the soft lining group. Conclusion: It appears that wearing dentures hinders blood flow to denture-supporting tissues, even when soft liners are used.