Background and objectives Characteristics of a nerve block depend on the distribution of local anesthetic (LA) close to the nerve. The relationship between longitudinal distribution of LA and nerve block characteristics has not been investigated in viv o, but one in vitro study showed decrements in action potential amplitudes with increasing exposure length. We describe the influence of longitudinal neural exposure to LA on nerve block duration adjusted for other likely influential factors. Methods We analyzed data from an ethical board approved prospective consecutive collected dataset of 180 healthy volunteers with a common peroneal nerve block (2.5-20 mL, 5-40 mg of ropivacaine). Data were retrieved from three independent randomized controlled trials. The longitudinal neural exposure to LA in millimeters was evaluated using ultrasound. Interventional covariates and demographics were retrieved. Nerve block duration, the dependent variable in the primary assessment, was defined as time of insensitivity to a cold stimulus and was evaluated blinded to all other covariates. Using a multiple linear mixed-effects model, we explored the association between neural exposure to LA and nerve block duration. Results We found a significant positive association between longitudinal neural exposure to LA and block duration (p<0.01). A 10% increase in longitudinal exposure resulted in an 8.7 (2.5; 15) min increase in block duration. LA dose was associated to block duration (p<0.001) but LA volume had no impact (p=0.93). Conclusions Longitudinal neural exposure to LA was significantly associated with nerve block duration. LA dose was the strongest determinant for block duration whereas LA volume had no influence.