Operating conditions strongly affect the productivity of photobioreactors (PBRs). Even though it is demonstrated that continuous systems allow higher biomass productivity, the use of the semicontinuous mode is more widespread for technological reasons. However, even on such a system, tuning the residence time can improve production, in particular if the solid retention time (SRT) is adjusted. Conversely, the hydraulic residence time (HRT) should be set to minimize nutrient loss. In this work, a previously implemented model was applied to a 3.4 m 3 , artificially illuminated pilot plant cultivating Arthrospira platensis, to define the best operating conditions in terms of SRT, which is often neglected in the common operating procedures. This new approach that combines modeling and management of operating conditions allowed obtaining a biomass productivity of 0.8 g L −1 day −1 , more than 3 times higher than that obtained in the same system operated with standard procedures (0.24 g L −1 day −1 ), even though the stability of the production is strongly related to the efficiency of the separation system. The SRT also influenced the protein content of the biomass, which was found to increase at lower residence times. Finally, by optimizing the culture medium in terms of the carbonate/bicarbonate ratio, a higher CO 2 exploitation was obtained.