We study injection molding of mesoscale items with µm‐scale surface features, namely micro‐fluidic channels, relating replication quality to process conditions. Using variothermal molding, the variables are the pre‐heat temperature of the cavity insert surface before melt injection and the mold cooling start time. Surface temperatures and in‐cavity melt pressures are continuously measured. Rounded upper corners of the micro‐channels are used as an index of replication quality. For polymethylmethacrylate the thickness of a layer with solid‐like properties (below 124°C) is calculated and used with pressures to interpret results. It is shown how improved replication correlates with low layer thickness at the end of the compression phase when pressures are at a maximum, and the necessity of properly timed cooling to lock in replication before melt pressures fall. Results show how the inter‐relationship of layer thickness and melt pressure is controlled by pre‐heat temperature and cooling switch‐on time. Delayed cooling can result in poorer replication, due to a retraction effect of the plastic. Too early cooling also reduces replication of parallel‐to‐flow features downstream of transverse features, and of the replication of transverse features on their downstream side. Good replication of 100 and 70 µm channels requires lower pre‐heat than 400 µm ones. POLYM. ENG. SCI., 58:1726–1738, 2018. © 2017 Society of Plastics Engineers