Purpose: To compare muscle thickness and 10-repetition maximum (10RM) between no load reduction and load reductions during 16 wk of resistance training. Methods: A total of 21 moderately trained men (age 23.2 [4.2] y, body mass 75.1 [7.6] kg, height 175 [4] cm) were randomized into 1 of 3 exercise groups: control (CON, n = 7), all sets with 10RM load; 5% load reduction (RED 5, n = 7); and 10% load reduction (RED 10, n = 7) for set 2 and set 3. The resistance training program consisted of completing 3 sets each of biceps and Scott curls, performed to volitional fatigue 3 d·wk−1. Results: Volume load lifted over the 16 wk was similar among groups (CON, 38,495 [4397] kg; RED 5, 37,388 [3684] kg; RED 10, 42,634 [6733] kg; P = .094). Muscle thickness increased in all groups (P < .001), with no differences noted among groups (P = .976). Biceps-curl and Scott-curl 10RM increased in all groups (P < .001), with no differences noted among groups (Scott curl P = .238; biceps curl P = .401). Rating of perceived exertion (RPE) was significantly lower for RED 10 (6.8 [0.1]) than for CON (7.0 [0.1]; P < .001) or RED 5 (7.1 [0.1]; P = .001) for the Scott curl. RPE was significantly lower (P = .001) for the biceps curl in RED 10 (6.8 [0.3]) than in CON (7.3 [0.9]), with neither group different from RED 5 (7.0 [0.1]). Conclusions: Load reduction did not yield a difference in hypertrophy or 10RM as compared with CON. However, RED 10 induced a significantly lower RPE. Thus, load reduction may be a beneficial strategy to reduce the perception of effort during training while achieving similar improvements in hypertrophy and strength.