Background: The use of immediate loading (IML) is still poorly explored in elderly patients and implant-retained mandibular overdenture (IMO) wearers. For this reason, more comparisons to conventional loading (CL) are required. Purpose: To evaluate the clinical, biological, functional, and oral health-related quality of life (OHRQOL) influence of CL and IML loading on elders wearing IMO retained by the Facility-Equator system up to 1 year after implant installation. Material and Methods: Twenty edentulous patients received two narrow diameter implants in the mandible; the loading type (CL or IML) was randomized. The clinical parameters were monitored along with prosthetic events, marginal bone loss (MBL) and bone level change (BLC), implant stability quotients (ISQ), masticatory performance outcomes, and Interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) levels in the peri-implant crevicular fluid during the first year of loading. The OHRQoL was assessed via the Oral Health Impact Profile-EDENT questionnaire. Data were analyzed by the Mann-Whitney, χ 2 , Wilcoxon paired, and McNemar tests. Results: After 1 year, MBL, BLC and ISQ were statistically identical (P > .05) in the CL and IML groups. The probing depth at 12 months in the CL group (2.19 mm) was higher than in the IML group (1.29 mm; P ≤ .0001). TNF-α was 33.6% higher in the CL group at 6 months (P = .043), while IL-1β was significantly higher in the IML group up to 6 months. The survival rate was 90% in the CL group and 85% in the IML group; 33 prosthetic events occurred in CL group and 23 in IML group. Conclusions: After 12 months, both loading protocols are viable and result in similar clinical, biological, functional, and OHRQOL outcomes. However, IML generates better adaptation of the peri-implant tissues, faster improvement in OHRQoL and fewer prosthetic intercurrences than CL.