A new mathematical model is developed to predict the fatigue life of Shielded Metal Arc Welded (SMAW) cruciform joints containing Lack of Penetration (LOP) defect. High strength, quenched and tempered steel (ASTM 517 ‘F’ Grade) is used as the base material throughout the investigation. Four factors, five level, central composite, rotatable design matrix is used to optimise the required number of experiments. Fatigue experiments have been conducted in a mechanical resonance pulsator, under constant amplitude loading. The model is developed by Response Surface Method (RSM). Analysis of Variance (ANOVA) technique is applied to check the validity of the model. Student’s t-test is utilised to find out the significant factors. The effect of joint dimensions on fatigue life have been analysed in detail.