Combining non-fullerene acceptors (NFAs) with novel low band gap polymers has led to very promising performances. However, research on donors that can reduce the performance–cost gap, such as poly(3-hexylthiophene) (P3HT), can play an instrumental role in the upscaling of this technology. In this paper, we have analysed the influence of several processing parameters on the performance of solar cells based on P3HT:NFA binaries deposited by blade coating. The investigated NFAs include molecules with variations in the side chains and end-capping groups. More precisely, we have looked at devices based on P3HT blended with five NFAs, namely ITIC, ITIC-M, O-IDTBR, EH-IDTBR, and O-IDFBR, and employed PC₆₀BM and ICBA as reference acceptors. More than one thousand doctor-bladed P3HT:NFA samples were manufactured using high throughput techniques using gradients of both thickness and annealing temperature. The combined data for all samples were employed to perform a parameter sensitivity study in order to identify the most influential parameters for P3HT based devices. For all material combinations, we have found that blade coated solar cells fabricated from chlorobenzene/dichlorobenzene mixtures outperform those based on chlorobenzene. For the most promising binary (i.e. P3HT:O-IDTBR), we have investigated in more depth the effects resulting from the choice of solvent, as well as casting temperature and post-deposition thermal annealing. Devices with power conversion efficiencies greater than 5% were obtained regardless of the casting temperature and for a relatively wide thickness range (80–250 nm). Finally, we have shown that encapsulated devices exhibit a stable performance for more than 3000 h and that degradation progresses faster in thicker devices. O-IDTBR has been identified to play a major role in the device degradation.