Membrane　wetting　is　one　of　the　key　challenges　that　needs　to　be　overcome　to　realize　operational　stability　in　membrane　distillation.　In　this　work,　we　showed　that　negative　pressure　mode　can　be　applied　into　direct　contact　membrane　distillation　(DCMD)　using　PVDF　hollow　fiber　membrane　to　achieve　such　stability　for　low　surface　tension　(42.2　mN　m−1)　organic　solvent　(represented　by　ethanol)-containing　saline　solution　feed　but　is　less　useful　for　surfactant　(represented　by　Tween-20)-containing　saline　solution　feed　with　similar　surface　tension.　While　the　conventional　positive　pressure　DCMD　showed　rapid　deterioration　of　flux　and　increase　of　permeate　conductivity　during　6-hour　continuous　operation　when　treating　a　25　vol%　ethanol　in　0.6　M　NaCl　solution,　negative　pressure　DCMD　could　maintain　stable　high　flux　of　10.4　kg　m−2　h−1　and　low　permeate　conductivity　of　3　μS　cm−1　throughout　6-hour　duration.　Using　time-dependent　droplet　evaporation　experiments　and　membrane　morphology　observations,　we　demonstrated　the　different　membrane　wetting　and　fouling　mechanisms　of　ethanol　and　Tween-20-containing　solutions.　We　also　demonstrated　that　negative　pressure　can　effectively　prevent　the　membrane　wetting　in　ethanol　solution　feed　case　by　keeping　the　contact　angle　of　the　liquid　on　the　pore　wall　larger　than　90o,　which　promotes　the　formation　of　a　Cassie-Baxter　state　on　the　liquid-vapor　interface.　©　2023