Wheat production needs to increase in coming years to supply food demand. An alternative to achieve this goal is to increase cultivar’s potential yield through genetic improvement. Spike fruiting efficiency (FE), defined as the grain number (GN) produced per unit spike dry weight at anthesis (SDW), is a promising trait to improve potential yield. It is the result of the fertile floret efficiency (FFE-number of fertile florets per unit SDW) and grain set (grains per fertile floret). As it is hard to measure, it is usually estimated at maturity (FEm) as the GN produced per unit of no-grain spike dry weight at maturity or chaff (CH). Previously we detected at the spike level the QFFE.perg-5A (associated with FFE, FE and FEm) and the QFEm.perg-3A (associated with FEm) in a doubled haploid (DH) population (Baguette19xBioINTA 2002, B19xB2002). In this study, we scaled up analyzing the impact of those QTL on yield and related traits. The DH was phenotyped at plot level (m-2) for FE, FEm, GN, SDW, CH, thousand grain weight (TGW) and spike number in 2 or 3 environments, depending on the trait. An ANOVA using the SNP of the QTL peak was performed to analyze the epistatic interactions and their effects on each trait. As a result, no epistatic interaction between QFFE.perg-5A and QFEm.perg-3A was detected (P>0.05). The QFFE.perg-5A did not present interaction with the environment in any of the studied traits (P>0.05). The presence of the B19 allele increased yield (615 vs 576 g m-2, P<0.05). As expected, the FE m-2 and FEm m-2 were higher when this allele was present, which was positively associated with the GN m-2. Interestingly, the number of spikes m-2 was similar or higher when the B19 allele was present without any significant impact the SDW m-2 and the TGW. For the QFEm.perg-3A, the B19 allele showed interaction with the environment, increasing the yield only in one environment. This response was accompanied by the number of spikes m-2 and the FE m-2, despite the FEm m-2 was superior in all environments. The SDW m-2 was not modified by the presence of this allele, but the TGW was reduced. These QTL could be used in marker assisted selection in early stages of a breeding program to select for spike fruiting efficiency in a quickly, simply, and cheap way, with the objective of increasing the rate of yield improvement.