Background We hypothesized that both perineural and systemic dexamethasone as adjuncts to bupivacaine increase the duration of an ulnar nerve block compared with bupivacaine alone, and that systemic dexamethasone is non-inferior to perineural dexamethasone. Methods We performed bilateral ulnar nerve blocks with 3 ml bupivacaine 5 mg/ml in 16 healthy volunteers on two trial days. According to randomization, subjects received adjunct treatment with 1 ml dexamethasone 4 mg/ml + 1 ml of saline (perineural condition) in one arm and 2 ml saline in the other arm (systemic condition, through absorption and redistribution of the contralaterally administered perineural dexamethasone) on one trial day; and 2 ml of saline in one arm (placebo condition) and 2 ml of lidocaine in the other arm (lidocaine condition) on the other trial day. The primary outcome was the duration of the sensory nerve block assessed by temperature discrimination. Results Mean sensory block duration was 706 ± 94 minutes for the perineural condition, 677 ± 112 minutes for the systemic condition, and 640 ± 121 minutes for the placebo condition. The duration of the sensory nerve block was greater with perineural dexamethasone versus placebo (mean difference (MD) 66 minutes (95% CI 23 to 108). Block duration was similar between systemic dexamethasone and placebo (MD 36 minutes; 95% CI -30 to 103). Conclusion Perineural dexamethasone as an adjunct to bupivacaine in healthy volunteers resulted in a greater duration of an ulnar nerve block when compared with placebo. Systemic dexamethasone resulted in a similar duration as placebo.