Sexual incompatibility among kola genotypes accounted for over 50% yield loss. Compatible and high yielding varieties are in demand to develop commercial orchards. The objective of this study was to assess self-compatibility and cross-compatibility of kola (C. nitida) genotypes within self, single and double hybrid crosses and to determine heterosis pattern in the resulting hybrids for sexual compatibility and key nut yield and quality traits. Crosses among kola genotypes from three field gene banks (JX1, GX1, MX2) and one advanced germplasm (Bunso progeny) in Ghana were evaluated along their parents for sexual compatibility, nut yield and nut quality. Data were collected on pod set, pseudo-pod set, pod weight, number of nuts per pod, nut weight, brix, potential alcohol and nut firmness. Significant (P < 0.001) differential pod set was observed within Bunso progeny, JX1, GX1 and MX2 crosses; while pseudo-pod set differed only within JX1 and MX2 crosses (P < 0.001). Very large prevalence of mid-parent, heterobeltiosis, and economic heterosis was observed for sexual compatibility, outturn and brix for the single and double hybrid crosses. Heterosis was prominent among the double hybrid crosses as compared to the single hybrid crosses suggesting that recurrent selection of compatible varieties from advanced generations could result in genetic gain in kola improvement. The top five crosses with best heterosis for sexual compatibility and an appreciable positive heterosis for outturn and brix were B1/11 × B1/71 × B1/157 × B1/149, B1/11 × B1/71 × B1/296 × B1/177, GX1/46 × GX1/33 × B1/212 × B1/236, JX1/90 × JX1/51 and JX1/51 × JX1/36. These materials could serve as sources of beneficial alleles for improving Ghanaian kola hybrids and populations for yield and sexual compatibility.