The origin of the odd-even effect in properties of self-assembled monolayers (SAMs) and/or technologies derived from them is poorly understood. We report that hydrophobicity and, hence, surface wetting of SAMs are dominated by the nature of the substrate (surface roughness and identity) and SAM tilt angle, which influences surface dipoles/orientation of the terminal moiety. We measured static contact angles (θs) made by water droplets on n-alkanethiolate SAMs with an odd (SAM(O)) or even (SAM(E)) number of carbons (average θs range of 105.8-112.1°). When SAMs were fabricated on smooth "template-stripped" metal (M(TS)) surfaces [root-mean-square (rms) roughness = 0.36 ± 0.01 nm for Au(TS) and 0.60 ± 0.04 nm for Ag(TS)], the odd-even effect, characterized by a zigzag oscillation in values of θs, was observed. We, however, did not observe the same effect with rougher "as-deposited" (M(AD)) surfaces (rms roughness = 2.27 ± 0.16 nm for Au(AD) and 5.13 ± 0.22 nm for Ag(AD)). The odd-even effect in hydrophobicity inverts when the substrate changes from Au(TS) (higher θs for SAM(E) than SAM(O), with average Δθs |n - (n + 1)| ≈ 3°) to Ag(TS) (higher θs for SAM(O) than SAM(E), with average Δθs |n - (n + 1)| ≈ 2°). A comparison of hydrophobicity across Ag(TS) and Au(TS) showed a statistically significant difference (Student's t test) between SAM(E) (Δθs |Ag evens - Au evens| ≈ 5°; p < 0.01) but failed to show statistically significant differences on SAM(O) (Δθs |Ag odds - Au odds| ≈ 1°; p > 0.1). From these results, we deduce that the roughness of the metal substrate (from comparison of M(AD) versus M(TS)) and orientation of the terminal -CH2CH3 (by comparing SAM(E) and SAM(O) on Au(TS) versus Ag(TS)) play major roles in the hydrophobicity and, by extension, general wetting properties of n-alkanethiolate SAMs.