When two indistinguishable single photons impinge at the two inputs of a beam splitter they coalesce into a pair of photons appearing in either one of its two outputs. This effect is due to the bosonic nature of photons and was first experimentally observed by Hong, Ou and Mandel 1 . Here, we present the observation of the Hong-Ou-Mandel effect with two independent single-photon sources in the microwave frequency domain. We probe the indistinguishability of single photons, created with a controllable delay, in time-resolved secondorder cross-and auto-correlation function measurements. Using quadrature amplitude detection we are able to resolve different photon numbers and detect coherence in and between the output arms. This scheme allows us to fully characterize the two-mode entanglement of the spatially separated beam-splitter output modes. Our experiments constitute a first step towards using two-photon interference at microwave frequencies for quantum communication and information processing 2-5 .So far, Hong-Ou-Mandel (HOM) two-photon interference has been demonstrated exclusively using photons at optical or telecom wavelengths. Experiments were performed with photons emitted from a single source using parametric downconversion 1 , trapped ions 3 , atoms 6 , quantum dots 7 and single molecules 8 . The HOM effect has also been observed with two independent sources 9-15 realizing indistinguishable single-photon states, which are required as a resource in quantum networks or linear-optics quantum computation. Such experiments have also been performed using donor impurities as sources 16 including nitrogen-vacancy centres in diamond (see ref. 17 and references therein). Furthermore, the HOM effect has been employed to create entanglement between ions 18 in spatially separated traps, and to realize a controlled-NOT gate in a small-scale photonic network 19 . Similar physics is also actively explored with ballistic electrons in solids (see ref. 20 and references therein).Here, we demonstrate the HOM interference of two indistinguishable microwave photons emitted from independent triggered sources realized in superconducting circuits (see Methods). The photons are prepared in two separate microwave resonators A (B) using transmon-type qubits and decay exponentially at rates κ/2π = 4.1 (4.6) MHz through their strongly coupled output ports into the input modesâ andb of the beam splitter (see Fig. 1). The two photons then interfere at the beam splitter and are emitted into the output modesâ andb (see Fig. 1a). Using the dispersive interaction between qubit and resonator, we tune the emission frequencies of the two sources to an identical value of ν r = 7.2506 GHz. For our experiments, we sequentially create 20 single photons in each source at a rate 1/t r = 1/512 ns ∼ 1.95 MHz in a sequence repeated every 12.5 µs.To probe the photon statistics in the beam-splitter output modesâ andb we use two spatially separated heterodyne detection channels 21,22 (see dashed rectangle in Fig. 1b). Each channel consists of a set of...