Whole-body electromyostimulation (WB-EMS) is commercially advertised as a time-efficient resistance-type exercise technology. Indeed, the commercial, non-medical setting applies 20 min of WB-EMS only once a week. However, this setting conflicts with the approved scientific approach of higher training frequencies. Using data from an ongoing study on WB-EMS and golf performance as a vehicle, we evaluate the effect of once weekly WB-EMS on changes of fatty muscle infiltration, as a crucial parameter of muscle quality. Fifty-four moderately physically active male amateur golfers 18–70 years old were randomly allocated to a WB-EMS (n = 27) with a standard setting of once weekly 20 min and a non-WB-EMS control group (CG, n = 27). Intermuscular adipose tissue (IMAT) volume and intrafascial muscle tissue (MT) volume per unit of intrafascial volume as determined by magnetic resonance imaging were used to characterize muscle quality. Intention to treat analysis with multiple imputation was applied. WB-EMS was conducted at the participants’ homes; thus, the attendance rate was close to 100%. After 16 weeks of intervention, we observed increases in volume-adjusted IMAT (p = 0.040) and decreases in MT (p = 0.206) in the CG. IMAT decreased in the WB-EMS group (p = 0.215), while MT increased significantly (p = 0.032). Of importance, group difference (i.e., “effects”) for intra-group changes in volume-adjusted IMAT (effect size: d´ = 0.66; p = 0.028) and MT (d´ = 0.70; p = 0.020) was significant for both parameters. Once weekly WB-EMS application significantly affects muscle quality of the mid-thigh in moderately active, healthy men 18–70 years old.