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& #x003b2;₃-adrenergic receptor (β₃-AR) activation produces a negative inotropic effect in human ventricles. Here we explored the role of β₃-AR in the human atrium. Unexpectedly, β₃-AR activation increased human atrial tissue contractility and stimulated the L-type Ca²⁺ channel current (I_Ca,L) in isolated human atrial myocytes (HAMs). Right atrial tissue specimens were obtained from 57 patients undergoing heart surgery for congenital defects, coronary artery diseases, valve replacement, or heart transplantation. The I_Ca,L and isometric contraction were recorded using a whole-cell patch-clamp technique and a mechanoelectrical force transducer. Two selective β₃-AR agonists, SR58611 and BRL37344, and a β₃-AR partial agonist, CGP12177, stimulated I_Ca,L in HAMs with nanomolar potency and a 60%–90% efficacy compared with isoprenaline. The β₃-AR agonists also increased contractility but with a much lower efficacy (~10%) than isoprenaline. The β₃-AR antagonist L-748,337, β₁-/β₂-AR antagonist nadolol, and β₁-/β₂-/β₃-AR antagonist bupranolol were used to confirm the involvement of β₃-ARs (and not β₁-/β₂-ARs) in these effects. The β₃-AR effects involved the cAMP/PKA pathway, since the PKA inhibitor H89 blocked I_Ca,L stimulation and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) strongly increased the positive inotropic effect. Therefore, unlike in ventricular tissue, β₃-ARs are positively coupled to L-type Ca²⁺ channels and contractility in human atrial tissues through a cAMP-dependent pathway.