Spin-orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers( PSs). Herein, as eries of perylene-Bodipy compact electrond onor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studiedw ith steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield F T = 60 %) waso bserved, with at riplets tate lifetime (t T = 436 ms) much longert han that accessed with the conventional heavy atom effect (t T = 62 ms). The SOCT-ISC mechanism wasu nambiguously confirmed by direct excitation of the charget ransfer (CT) absorption band by using nanosecond transienta bsorption spectroscopy and time-resolved electronp aramagnetic resonance (TREPR) spectroscopy.T he factors affecting the SOCT-ISC efficiency include the geometry,t he potential energy surfaceo ft he torsion, the spin density for the atoms of the linker,s olvent polarity,a nd the energym atchingo ft he 1 CT/ 3 LE states. Remarkably,t hese heavya tom-free triplet PSs were demonstrated as an ew type of efficient photodynamic therapy (PDT) reagents (phototoxicity,E C 50 = 75 nm), with an egligibled ark toxicity (EC 50 = 78.1 mm)c ompared with the conventionalh eavy atom PSs (dark toxicity,E C 50 = 6.0 mm, light toxicity, EC 50 = 4.0 nm). This study provides in-depthu nderstanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, andu nderlines their applicationa sanew generationo fp otent PDT reagents.[a] Dr.[h] Prof. M. Di Donato INO, Istituto Nazionale di Ottica Largo Enrico Fermi 6, 50125F lorence (Italy)[ + + ] These authorscontributed equally to this work.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.