Purpose: The aim of this research was to determine the long-term prosthodontic maintenance requirements of mandibular two-implant overdentures using different loading protocols and attachment systems. Materials and Methods: A total of 106 participants were allocated randomly to one of four different implant systems (Steri-Oss, Southern, Straumann, or Brånemark). Three different loading protocols (2, 6, and 12 weeks) were used with six different ball abutment patrices and their respective matrices (Steri-Oss rubber, Straumann gold, Straumann titanium, Brånemark gold, Southern plastic, and Southern gold/platinum). Prosthodontic maintenance events were documented prospectively from baseline until the 8-year recall according to predefined categories. Results: After 6 years, 90 participants attended recall and, thereafter, 68 participants were followed for 8 years. No significant differences were found between the number of prosthodontic maintenance events and the loading protocol used. Steri-Oss rubber matrices had the highest mean number of maintenance events at 32.2 ± 14.5 events, followed by the Brånemark gold matrices at 28.8 ± 12.6 events. The Southern plastic matrices had a significantly lower mean number of maintenance events (8.7 ± 4.2) when compared with all other groups. Over a 6-year period, the matrices with the best longevity were Straumann gold at 3.9 ± 2.1 years. Straumann gold matrices also lasted significantly longer than all other matrices (P .05). Southern gold/platinum, Brånemark gold, and Southern plastic matrices all lasted significantly longer than the Straumann titanium and Steri-Oss matrices (P .05). The mean time to reline for overdentures was 3.37 ± 2.06 years; remaking of overdentures peaked by year 7, with a mean time to remake of 5.81 ± 2.04 years. Conclusion: Early loading protocols do not influence long-term prosthodontic maintenance requirements of unsplinted mandibular two-implant overdentures. By contrast, attachment systems do influence prosthodontic maintenance, particularly with regard to the type of matrices used.