It has been proposed that inbreeding and selection in cultivated alfalfa (Medicago sativa L.) may increase the frequency of alleles with favorable effects. Inbred lines of cultivated alfalfa at the diploid level (CADL, 2n = 2x = 16) were developed by selfing (S), sib‐mating (SM), and composite S1 sib‐mating (S1SM). Dry matter yield of field grown spaced‐plants from the F1, S1, S2, SM1, SM4, and S1SM3 generations was harvested twice in a single year to determine inbreeding effects and if favorable alleles were accumulated while inbreeding. Plant vigor and fertility declined significantly (P < 0.01) in most advanced generations. Inbreeding depression under selfing was equal to or less than the percent change in the coefficient of inbreeding, F. One family survived five generations of self‐pollination (F = 0.97). Inbreeding depression under sib‐mating often exceeded the percent change in F by as much as twofold. The average rate of inbreeding depression, expressed as the percent change in yield for each percent change in F, was less under selfing (−0.80) than under sib‐mating (−1.91) although exceptions to the general trend did occur. Phenotypic improvement was never noted under exclusive selfing. Two sib‐mated generations tended to outperform earlier, less‐inbred generations, indicating that favorable alleles were accumulated while inbreeding.