The best way to reach Douro Valley from Lisbon is by Private Transfer.
From Lisbon, you can request pickup at your hotel/accommodation front door, or airport, with your luggage, directly to your destination in Douro Valley, without the hassle of public transportation and crowds. Specially because there are no direct trains.
Any destination place in the Douro Valley can be covered, some examples: Lamego, Peso da Regua, Pinhão, Mesão Frio, Resende, Marco de Canaveses, and much more.
We cover many hotels, such as: Six Senses Douro Valley, Douro Palace, Vintage House, Pacheca, Vila Galé, Quinta Nova, Delfim, Douro Royal, Scala, and much more.
There are three options to consider:
OPTION #1: Direct Transfer (Private), no stops (by LisbonGuide / Concierge Portugal): https://lisbonguide.org/private-transfers-portugal/
OPTION #2: Private Transfer, by Portugal Magik Tours: https://portugal-magik.com/tour/private-driver-transfer-from-lisbon-to-douro-valley-2/
OPTION #3: Car + Driver at your disposal with Portugal Magik (Ideally for multiple days): https://portugal-magik.com/tour/driver-portugal/
You can also follow here this app, for instant quotation and booking: https://lisbon.ridebitsapp.com/central/new_reservation
Enjoy Lisbon and Douro Valley. Make sure to travel in comfort and safety.