The objective of this study was to determine differences in 2 distinct resistance training protocols and if true variability can be detected after accounting for random error. Individuals (n = 151) were randomly assigned to 1 of 3 groups: (i) a traditional exercise group performing 4 sets to failure; (ii) a group performing a 1-repetition maximum (1RM) test; and (iii) a time-matched nonexercise control group. Both exercise groups performed 18 sessions of elbow flexion exercise over 6 weeks. While both training groups increased 1RM strength similarly (∼2.4 kg), true variability was only present in the traditional exercise group (true variability = 1.80 kg). Only the 1RM group increased untrained arm 1RM strength (1.5 kg), while only the traditional group increased ultrasound measured muscle thickness (∼0.23 cm). Despite these mean increases, no true variability was present for untrained arm strength or muscle hypertrophy in either training group. In conclusion, these findings demonstrate the importance of taking into consideration the magnitude of random error when classifying differential responders, as many studies may be classifying high and low responders as those who have the greatest amount of random error present. Additionally, our mean results demonstrate that strength is largely driven by task specificity, and the crossover effect of strength may be load dependent. Novelty Many studies examining differential responders to exercise do not account for random error. True variability was present in 1RM strength gains, but the variability in muscle hypertrophy and isokinetic strength changes could not be distinguished from random error. The crossover effect of strength may differ based on the protocol employed.