Recent concern about the consequences of continuing increases in atmospheric CO2 as a key heat-trapping agent (Wuebbles et al., 2017; Masson-Delmotte et al., 2021) has prompted ocean experts to come together to discuss how to provide science-based solutions. Ocean alkalinity enhancement (OAE) is being considered not only as an ocean carbon dioxide removal (CDR) approach but also as a potential way to mitigate ocean acidification. Over the last 2 decades, inter-laboratory comparisons have proven valuable in evaluating the reliability of methodologies associated with sampling and analysis of carbonate chemistry parameters, which have been routinely used in ocean acidification research. Given the complexity of processes and mechanisms related to ecosystem responses to OAE, consolidating protocols to ensure compatibility across studies is fundamental for synthesis and upscaling analysis. This chapter provides an overview of best practice in OAE laboratory experimentation and facilitates awareness of the importance of applying standardized methods to promote data re-use, inter-lab comparisons, meta-analysis and transparency. This chapter provides the reader with the tools to (1) identify the criteria to achieve the best laboratory practice and experimental design, (2) provide guidance on the selection of response variables for various purposes (physiological, biogeochemical, ecological, evolutionary) for inter-lab comparisons, (3) offer recommendation for a minimum set of variables that should be sampled and propose additional variables critical for different types of synthesis and upscaling, and (4) identify protocols for standardized measurements of response variables. Key recommendations include ensuring reproducibility through appropriate experimental design and replication, assessing alkalinity thresholds for secondary precipitates for each experimental approach and condition, using recommended targets of alkalinity (3000–4000 µmol kg−1) and levels exceeding these concentrations to mimic responses at the site of deployment/non-equilibrium and to use intermediate alkalinity levels to identify potential nonlinear responses, and establishing the appropriate experimental design to address questions at specific levels of organization (chemical, physiological, molecular) and assuming different scenarios (e.g., mimicking impacts at the site of deployment in a non-equilibrated system versus steady-state scenarios in an equilibrated system).