Simão, R, Polito, M, de Salles, BF, Marinho, DA, Garrido, ND, Santos Junior, ERT, and Willardson, JM. Acute and long-term comparison of fixed vs. self-selected rest interval between sets on upper-body strength. J Strength Cond Res 36(2): 540–544, 2022—The effects of different rest interval durations between sets has been widely studied, but only recently, the self-selected rest interval (SSRI) has been a matter of interest. However, previous studies comparing fixed and SSRI have investigated only acute responses. The purpose of this study was to analyze the acute and long-term effects of a fixed rest interval (FRI) vs. an SSRI between sets on upper-body performance and strength gains. Thirty-three trained men were randomly divided into 2 groups: FRI (75 seconds between sets), and SSRI. Both groups performed 3 sets with 75% of 1-repetition maximum until repetition failure in the chest press (CP), lat pull-down (LPD), shoulder press (SP), and seated row (SR) 3 times a week for 8 weeks. The results demonstrated that the SSRI allowed for significantly greater repetition performance vs. the FRI in the CP (26.1 ± 2.0 vs. 21.5 ± 1.8), LPD (30.1 ± 2.3 vs. 24.9 ± 1.9), SP (24.0 ± 2.8 vs. 17.4 ± 1.5), and SR (26.3 ± 1.6 vs. 22.0 ± 1.6). In addition, the following strength gains were observed: SSRI (CP: 6.8%, LPD: 8.0%, SP: 6.7%, SR: 7.8%) and FRI (CP: 7.4%, LPD: 6.7%, SP: 6.1%, SR: 7.0%) without significant differences between the groups. In conclusion, within an 8-week period, both protocols seem to be effective for strength gains, despite the higher training volume accomplished by the SSRI group. However, the FRI was 37% more time efficient.