Our aim was to establish the determinants explaining the wetsuit advantages in middle-distance swimming efforts. Thirty-one triathletes and open water swimmers performed two 400m front crawl bouts in a 25m swimming pool with swim and wetsuits (with 48h rest in-between). Anthropometric, kinematic and physiological variables were measured and Pearson correlation coefficients and stepwise linear regression analysis used to determine their relationships. Associations were observed in the 400m front crawl time improved using wetsuit with swimmers age (r=0.38;p=0.017), cross-sectional area (r=0.33;p=0.034), wetsuit upper limbs thickness (r=-0.49;p=0.010), ΔInternational Swimming Federation Points (r=-0.39;p=0.016), Δstroke rate (SR, r=0.48;p=0.003), Δstroke length (SL, r=-0.39;p=0.015), Δpropelling efficiency (r=-0.37;p=0.019) and Δblood lactate concentrations (r=0.30;p=0.048) in the total sample. In females, associations were found between the time improved and wetsuit upper and lower limbs thickness (both r=-0.78;p=0.011) and in males between this time improved and age (r=0.43;p=0.030), ΔSR (r=0.56;p=0.005) and ΔSL (r=-0.44;p=0.026). Furthermore, 48% of the 400m front crawl time improved was explained by wetsuit upper limbs thickness and SR changes (total sample), 62% explained by the wetsuit lower limbs thickness (females) and 48% of this enhancement was related to age and SR changes (males). Therefore, faster upper and lower limbs actions and wetsuit upper and lower limbs thickness are beneficial for 400m front crawl performance improvement.