The effects of an enforced fast start on long-distance performance are controversial and seem to depend on the athlete’s capacity to delay and tolerate metabolic disruption. The aim of this study was to investigate the effects of an enforced start on 10-km-running performance and the influence of the some physiological and performance variables on the ability to tolerate an enforced fast start during the running. Fifteen moderately trained runners performed two 10-km time trials (TTs): free pacing (FP-TT) and fast start (FS-TT). During FS-TT, speed during the first kilometer was 6% higher than in FP-TT. Maximal oxygen uptake (VO2max), peak velocity (PV), velocity associated with VO2max (vVO2max), ventilatory threshold, and running economy at 10 and 12 km/h and FP-TT average velocity (AV-10 km) were individually determined. There were no differences between FP-TT and FS-TT performance (45:01 ± 4:08 vs 45:11 ± 4:46 min:s, respectively, P = .4). Eight participants improved (+2.2%) their performance and were classified as positive responders (PR) and 7 decreased (–3.3%) performance and were classified as negative responders (NR). Running speed was significantly higher for PR between 6 and 9.2 km (P < .05) during FS-TT. In addition, PR presented higher PV (P = .02) and vVO2max (P = .01) than NR, suggesting that PV and vVO2max might influence the ability to tolerate a fast-start strategy. In conclusion, there was an individual response to the enforced fast-start strategy during 10-km running, and those who improved performance also presented higher vVO2max and PV, suggesting a possible association between these variables and response to the strategy adopted.