PROBLEM: Sex-specific responses to an acute bout of resistance exercise (RE) are unknown. The purpose of the present study was to determine sex-specific responses to an acute bout of RE on heart rate variability (HRV) and heart rate complexity (HRC). METHODS: Twenty-three resistance-trained men (n=13) and women (n=10) volunteered for the study. Autonomic modulation was assessed at rest, as well as 15-20 minutes (Rec1) and 25-30 minutes (Rec2) after an acute bout of RE utilizing 3 sets of 10 repetitions at 75% 1-repetition maximum on the squat, bench press and deadlift with two minutes of rest between sets. Measures of HRV were analyzed in the frequency domain and included measures of vagal modulation (normalized high frequency (HFnu)), sympathetic modulation (normalized low frequency (LFnu)), and sympathovagal balance (LF/HF ratio). Sample Entropy (SampEn), indicative of vagal modulation, was used as a measure of HRC. RESULTS: There were no significant sex differences at rest for any of the variables. Furthermore, there were no significant sex by condition by time interactions for any variable. Compared with Rest, LFnu (Rest: 35.5±15.3%; Rec1: 73.0±18.0; Rec2: 66.0±25.1%, p=0.0001), LnLF/HF (Rest: 4.0±0.9; Rec1: 5.1±1.1; Rec2: 5.2±1.1, p=0.002) were augmented at Rec1 and Rec2. HFnu (Rest: 61.2±17.1%; Rec1: 40.3±22.3%; Rec2: 38.4±21.8%, p=0.0001) and SampEn (Rest: 1.5±0.3units; Rec1: 1.2±0.3units; Rec2: 1.3±0.5units, p=0.0001) were decreased at Rec1 and Rec2 compared to Rest after the acute RE. CONCLUSION: These data suggest that acute RE using free-weights has a profound impact on autonomic modulation that is similar between the sexes.