STATEMENT OF PROBLEM: Evidence provided by implant-supported mandibular overdenture research on different loading protocols is important. However, methodological inconsistency, as well as inadequate reporting of results, hampers a consistent decision in terms of clinical applicability. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate whether immediate or early loading protocols can achieve comparable clinical outcomes when compared with a conventional loading protocol in edentulous patients rehabilitated with mandibular overdentures. MATERIAL AND METHODS: In accordance with the Participant, Intervention, Comparison, Outcome strategy, prospective clinical studies without restrictions as to language or follow-up period were included. The Cochrane collaboration and ROBINS-I tools were used for quality assessment and risk-of-bias evaluation. The follow-up for the different outcomes ranged from 3 to 168 months, with the focus on implant success and survival rates, marginal bone loss, bleeding on probing, probing depth, plaque index, and the implant stability quotient. Statistical analyses in which standard mean differences were applied with a 95% confidence interval when continuous data were included were performed. For dichotomous data, risk difference was adopted. RESULTS: The search strategy resulted in 14 234 references. Twenty-three studies fulfilled the inclusion criteria. Meta-analysis showed statistically significant differences for plaque index at 12 months (standard mean difference=0.284 [0.022, 0.545], P=.033, I2=35%), probing depth at 36 months (standard mean difference=0.460 [0.098, 0.823], P=.013, I2=0%), and on pooled results for plaque index (standard mean difference=0.157 [0.031, 0.284], P=.015, I2=18%) in which the conventional loading protocol presented lower indices than those of immediate loading protocol or early loading protocol. Implant stability quotient presented a statistically significant difference only at 3 months (standard mean difference=0.602 [0.309, 0.895], P<.001, I2=0%) with higher values for the conventional loading protocol. For the other parameters, statistically significant differences (P>.05) were not found. CONCLUSIONS: Immediate loading protocol or early loading protocolfor mandibular overdentures has been determined to be a well-established treatment and worthy of consideration in clinical practice.