High efficiency, power concentration and reliability are the main requirements from Diesel Engines that are used in most technical applications. This becomes more important with the increase of engine size. For this reason the aforementioned characteristics are of significant priority for both marine and power generation applications. To guarantee efficient engine operation and maximum power output, both research and commercial communities are increasingly interested in methods used for supervision, fault-detection and fault diagnosis of large scale Diesel Engines. Most of these methods make use of the measured cylinder pressure to estimate various critical operating parameters such as, brake power, fuel consumption, compression status, etc. The results obtained from the application of any diagnostic technique, used to assess the current engine operating condition and identify the real cause of the malfunction or fault, depend strongly on the quality of these data. The last are strongly affected by various parameters among which the most important is load which should be maintained constant during cylinder pressure measurement. For practical (i.e. complexity, etc) and financial reasons cylinders are measured consequently one after the other instead of simultaneously. Because of this, the estimated parameters for each cylinder depend on the instantaneous engine load which may vary during a measurement series. Therefore it is of significant importance to distinguish if a detected problem or mistuning is attributed to the cylinder condition or to random load variation during the measurement. Beyond this, uniform cylinder loading is extremely important for large diesel engines operating on the field in marine and land based applications. Uniform cylinder operation can be achieved reliably only if the actual power of each engine cylinder is determined on the field and then this information is used for tuning. The most effective method to estimate cylinder power is to conduct cylinder pressure measurements. But as already mentioned it is usually extremely difficult to simultaneously measure cylinder pressure to avoid the effect of power fluctuation during the measurement. For this reason an attempt is made in the preset work to propose and evaluate a new technique to detect load fluctuation during cylinder pressure measurement. Most importantly, its ability to “correct” the problem and produce results for cylinder loading that are equivalent to the ones that would have been derived if all cylinders were measured simultaneously is evaluated. To achieve this, an existing diagnostic technique, developed by the present research group, has been properly modified to account for load fluctuation during cylinder pressure measurement. To validate the method, measurements have been conducted on a large-scale four-stroke V-type diesel engine used for power generation in a Greek island, at various operating conditions. The technique is based on the simultaneous use of two cylinder pressure sensors one of which remains mounted on the same cylinder being thus the reference one. From the application of the technique, results are derived for cylinder load using both the conventional technique i.e. sequential cylinder pressure measurement and the newly proposed one. Their evaluation is based on the comparison of results referring to cylinder power output and the required tuning to achieve uniform cylinder loading. From the comparison of derived results it is demonstrated that the new technique identifies quite well load fluctuation and its effect on cylinder performance data. Furthermore, the ability of the technique to correct the derived results and propose a proper engine tuning to guarantee uniform cylinder operation is clearly revealed.