Local muscle endurance (LME) is a significant indicator of muscle health and function in middle-aged and older adults. However, resistance training (RT) practices which optimise performance in this population are currently unclear. This study examined: 1) the effect of RT on LME; and 2) the impact of acute resistance exercise program variables on LME in middle-aged and older adults. Five electronic databases were searched using terms related to RT, LME, and older adults. Random effects (Hedges' g) meta-analyses were undertaken to estimate the effect of RT on upper and lower body LME assessed via maximal repetitions during an isotonic test. The impact of resistance exercise program variables on LME effects was explored using meta-regression analyses. Fifteen studies met the inclusion criteria for this review. Upon sensitivity analysis, one study was removed. Large effects favoured RT for LME of the upper body (g = 1.10, p < 0.001) and lower body (g = 1.18, p < 0.001). Large effects on LME from RT were found irrespective of training intensity or other resistance exercise program variables. Moderate heterogeneity and publication bias were found in most analyses. RT is an effective means for improving LME in middle-aged and older adults. Optimal training characteristics have not been defined by this review, as improvement in LME was unrelated to RT volume or loading intensity. Caution is warranted when interpreting the findings due to heterogeneity and bias present in existing literature. Additional studies are needed with direct comparisons of various training techniques.