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Background/Objectives: Obesity is frequently associated with dyslipidemia, insulin re-sistance, and increased cardiovascular risk. Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), has been shown to improve metabolic outcomes; however, data integrating lipid profile changes with atherogenic and insulin resistance indices over extended follow-up remain limited. This study aimed to evaluate the longitudinal impact of RYGB on lipid parameters, atherogenic indices, and insulin resistance markers up to 18 months postoperatively. Methods: A longitudinal observational study was conducted in 40 adults with obesity (mean age 46.6 years; 82.5% women) undergoing RYGB. Bio-chemical and anthropometric data were collected preoperatively (E1) and at 6 (E3), 12 (E4), and 18 (E5) months after surgery. Lipid profile parameters, atherogenic indices (TG/HDL ratio, atherogenic indices Castelli I and Castelli II), and insulin resistance–related indices (TyG-BMI, MTS-IR) were analyzed descriptively over time. Results: RYGB induced a marked and sustained reduction in triglycerides, total cholesterol, and LDL cholesterol, alongside a progressive increase in HDL cholesterol. All atherogenic indices demon-strated consistent postoperative declines, indicating reduced cardiovascular risk. Insulin resistance indices showed pronounced improvement, particularly within the first 12 months, with stabilization thereafter. These metabolic benefits occurred in parallel with significant weight loss and reductions in central adiposity. Conclusions: Roux-en-Y gastric bypass promotes sustained improvements in lipid metabolism, atherogenic risk, and insulin resistance up to 18 months after surgery. The integration of lipid-derived and insulin resistance indices provides valuable insight into postoperative cardiometabolic risk reduction, supporting the role of bariatric surgery as an effective intervention for long-term cardiovascular risk mitigation.