Background: Running is a very popular activity and muscle strength imbalance has been treated with caution to prevent injuries. Aim: The present study aimed to compare and correlate knee flexion and extension strength imbalance based on peak torque (PT) and total work (TW) in running athletes. Methods: Thirty-eight male amateur running athletes (38 ± 6 years; 80.6 ± 8.3 kg; 177 ± 7 cm; 7.8 ± 8.4 years of training; 3.5 ± 0.9 training sessions a week; 33.5 ± 13.4 km of training per week) took part in the present study. Knee flexion eccentric and concentric PT and TW, as well as concentric knee extension PT and TW were assessed. PT- and TW-based hamstring-to-quadriceps ratios (H:Q), as well as PT and TW contralateral imbalance were quantified. Results: A significant correlation was observed between TW and PT concentric knee flexion contralateral deficits (r = 0.52, p < 0.001). No further correlations were found among TW- and PT-based muscle strength imbalance variables (p > 0.05). All mean comparisons of H:Q and contralateral imbalances using TW or PT were significantly different (p < 0.05). Conclusions: Our results showed that TW and PT muscle strength imbalance were unrelated, and the H:Q and contralateral imbalance profile of endurance runners may differ based on the isokinetic variable analyzed.