Objective To propose a regional iterative phase extraction Dixon method based on second order difference quality weighting (SOD-RIPE) for improving water-lipid separation in heterogeneous magnetic field. Method The in-phase angle of the asymmetric in-phase and opposite phase image matrix was eliminated using the Dixon's signal model to obtain J1 and J2, from which the possible water signal magnitude (B, S) and in-phase and opposite phase difference (P1, P2) was derived using the Cosine law. The phase quality map R of J2 was calculated using the second-order difference, and the phase difference was weighted to obtain (Pv, Pu). The Pv and Pu were iteratively selected to obtain the Pf. The water-fat separation diagram (W, F) was obtained using the least square method to bring the Pf into the Dixon signal model. Results Water-lipid separation was performed using 1000 pairs of in- and opposite-phase images on a Philips in Genia II 3.0T magnetic resonance scanner. The SOD-RIPE algorithm achieved better separation and stability than the automatic growth method and RIPE in all the parts of the body and in the stability test, and had a similar performance to mDixon-XD algorithm. Conclusion SOD-RIPE can achieve robust water-fat separation with a good stability and can be used as a general Dixon water-fat separation method.