Lipase-catalyzed acidolysis in hexane to produce structured lipids (SLs) from sesame oil and caprylic acid was optimized by considering both total incorporation (Y-1) and acyl migration (Y-2). Response surface methodology was applied to model Y-1 and Y-2, respectively, with three reaction parameters: temperature (Xi), reaction time (X-2), and substrate molar ratio (X-3). Well-fitting models for Y-1 and Y-2 were established after regression analysis with backward elimination and verified by a X-2 test. All factors investigated positively affected Y-1. For Y-2, X-1 showed the greatest positive effect. However, there was no effect of X-3. We predicted the levels of Y-2 and acyl incorporation into sn-1,3 positions (Y-3) based on Y-1. The results showed that over the range of ca. 55 mol % of Y-1, Y-3 started to decrease, and Y-2 increased rapidly, suggesting that Y-1, should be kept below ca. 55 mol % to prevent decrease in quality and yield of targeted SLs.