Why do greasy membrane proteins form stable complexes via greasy binding interfaces in the similarly greasy lipid solvent? To answer this question, we must quantify the thermodynamic factors that drive membrane protein association in membranes. Previously, we found that the CLC-ec1 Cl-/H+ antiporter participates in an equilibrium dimerization reaction in 2:1 POPE:POPG lipid bilayers. The dimer assembles via a large membrane embedded interface lined by non-polar residues, and the complex is stable, exhibiting a free energy of dimerization of −11 kcal/mole relative to the subunit/lipid standard state. Thus, CLC-ec1 provides an ideal model system for studying this question. In the current study, we carried out a van't Hoff analysis of the CLC-ec1 (WT) dimerization equilibrium in lipid bilayers. To verify that we are studying the equilibrated system, we examined subunit-exchange kinetics between WT-Cy3, and WT-Cy5 EPL (E. coli polar lipid) proteoliposomes, fused to form multi-lamellar membranes. Mixing of subunits led to formation of heterodimers (WT-Cy3/WT-Cy5) and the resulting increase in bulk Förster Resonance Energy Transfer (FRET) was monitored as a function of time, and temperature (22-56°C). Additionally, temperature jump type experiments conducted for the co-labelled WT showed changes in FRET, with both fused and co-labelled samples converging to the same FRET- plateaus. We found that rate of subunit-exchange increases with temperature, and that FRET- plateau decreases above 44oC indicating a decrease in oligomerization, with the chloride transport function remaining unchanged across the same temperature range. To measure the full dimerization binding isotherm, we equilibrated WT-Cy5 in EPL membranes at various temperatures and carried out subunit capture single-molecule photobleaching analysis for measurement of Keq(T). Finally, a van't Hoff plot of ln(Keq) vs. 1/T is presented, allowing a thermodynamic dissection of enthalpy, entropy, and heat capacity changes associated with CLC dimerization in membranes.