In this paper, the concept of Birkhoff-James orthogonality of operators on a Hilbert space is generalized when a semi-inner product is considered. More precisely, for linear operators T and S on a complex Hilbert space H, a new relation T ⊥ B A S is defined if T and S are bounded with respect to the seminorm induced by a positive operator A satisfying T + γS A ≥ T A for all γ ∈ C. We extend a theorem due to R. Bhatia and P.Šemrl, by proving that T ⊥ B A S if and only if there exists a sequence of A-unit vectors {x n } in H such that lim n→+∞ T x n A = T A and lim n→+∞ T x n , Sx n A = 0. In addition, we give some A-distance formulas. Particularly, we proveSome other related results are also discussed.