Bartolomei, S, Nigro, F, Malagoli Lanzoni, I, Masina, F, Di Michele, R, and Hoffman, JR. A comparison between total body and split routine resistance training programs in trained men. J Strength Cond Res 35(6): 1520–1526, 2021—The purpose of the present investigation was to compare the effects of total body (TB) versus split routine (SR) resistance training workouts on maximal strength and muscle hypertrophy in trained men. Twenty-one resistance-trained men were randomly assigned to either a TB (TB: age = 24.1 ± 4.4 years; body mass = 78.7 ± 11.3 kg; body height = 177.0 ± 3.9 cm) or the SR group (SR: age = 24.9 ± 4.2 years; body mass = 79.2 ± 9.5 kg; body height = 175.2 ± 6.0 cm). Both groups performed a 10-week resistance training program. Isokinetic bench press at 75 and 25 cm·s−1 (ISOK75 and ISOK25, respectively), isometric bench press (ISOBP), isometric squat (ISOSQ), and one repetition maximum BP and SQ assessments were performed before and after training. Muscle thickness of the pectoralis major (PECMT), superior part of trapezius (TRAPMT), and vastus lateralis (VLMT) muscles was also evaluated at the same timepoints using ultrasonography. Improvements were observed in both groups for all strength assessments and muscle thicknesses. Only changes in ISOK25 were significantly (p = 0.015) greater in TB than in SR, while significantly greater (p = 0.037) changes in VLMT were detected in SR compared with TB. Results indicated that a TB training paradigm may be more appropriate for maximal strength improvement, while an SR training protocol may be more optimal in stimulating muscle growth in experienced, resistance-trained men.