Introduction Research has shown that sustained-release (SR) dexamphetamine is a promising agonist treatment for cocaine dependence. However, little is known about the pharmacokinetics (PKs) of SR oral dexamphetamine. This study examined the PKs of a new SR dexamphetamine formulation in cocaine plus heroin-dependent patients currently in heroin-Assisted treatment. Methods The study was designed as an open-label PK study in 2 cohorts: n = 5 with once daily 60 mg and n = 7 with once daily 30 mg SR oral dexamphetamine. Five days of blood plasma dexamphetamine concentrations measured with liquid chromatography-mass spectrometry with PK parameter estimates using noncompartmental analysis. Results Twelve cocaine-dependent plus heroin-dependent patients in heroin-Assisted treatment were included. The initial cohort 1 dose of 60 mg once daily was adjusted to 30 mg after mild to moderate adverse events. After oral administration, tmax values (coefficient of variation %) were 6.0 (17.0%) and 6.3 (16.3%) hours and t1/2 were 11 (24.6%) and 12 (25.4%) hours for 60 mg and 30 mg SR dexamphetamine, respectively. At steady state, CSSmax values were reached at 100 (27.5%) ng/mL and 58.4 (14.4%) ng/mL, whereas CSSmin values were 39.5 (38.9%) ng/mL and 21.8 (19.8%) ng/mL for 60 mg and 30 mg, respectively. Conclusions The investigated SR formulation of dexamphetamine showed favorable slow-release characteristics in cocaine and heroin-dependent patients. A dose-proportional steady-state concentration was achieved within 3 days. These findings support the suitability of the SR formulation in the treatment of cocaine dependence.