This paper presents the results of an investigation through the design of experiment technique regarding the influence of temperature, dwell time and bar pressure on the heat seal strength of oriented polypropylene films coated with a gelatin-based thin layer. This chemometric approach allowed achieving a thorough understanding of the effect of each independent factor on the two different responses (maximum force and strain energy) considered in this work as a measure of the strength necessary to break the bond across the sealed interface. Surprisingly, the factor affecting both responses the most was the bar pressure rather than the sealing temperature. Moreover, whereas the bar pressure negatively affected the seal strength of coated polypropylene films, the sealing temperature had a positive effect. Dwell time did not have any significant influence as a main factor, while influencing negatively the seal strength as an interaction term (i.e. time × pressure), together with the further interaction temperature × pressure. The mathematical models obtained for the two responses provided different results in terms of fitting capability (R2) and prediction ability (Q2). In particular, for the maximum force response, R2 and Q2 were equal to 0.571 and 0.405, respectively, whereas the model supporting the strain energy response gave R2 = 0.932 and Q2 = 0.937, highlighting that for quantifying the seal strength, the energy necessary to break a seal is a better measure than the maximum force. The highest seal strength values obtained during this work were of 0.6615 N and 19.6 N·mm for maximum force and strain energy, respectively. Copyright © 2009 John Wiley & Sons, Ltd.